Welcome back to Last Week Tonight in BioPharma (LWTB). What a week!

This week, BMS wrote a $600M check to Hengrui as part of a staggering $15.2B China licensing deal. Novo dropped new obesity data showing high-dose WEGOVY hitting 28% weight loss in a group of fast-responders, but could this data actually speak to a long-term trend in obesity that backfires against Novo and Lilly? Meanwhile, BeOne get's its BCL-2 inhibitor BEQALZI across the FDA finish line for relapsed or refractory mantle cell lymphoma. Oh, and the FDA’s entire top-level of leadership got the axe.

All that and more below. Let’s get into it!

📡 PRESS RELEASE DECODER

What the press releases actually mean

FDA Grants Accelerated Approval to BeOne’s BEQALZI (sonrotoclax) for R/R Mantle Cell Lymphoma

📅 May 13, 2026 | 🏢 BeOne Medicines ( ) | 💊 BEQALZI (sonrotoclax) | 🏷 FDA Accelerated Approval

The FDA granted accelerated approval to BeOne Medicines’ ($ONC) BEQALZI (sonrotoclax) for relapsed or refractory mantle cell lymphoma (R/R MCL) on May 13, making it the first and only BCL-2 inhibitor cleared in this indication. The approval marks the 14th novel drug FDA has approved so far in 2026, per the agency’s running tally.

Sonrotoclax is a next-generation BCL-2 inhibitor designed to address some of the resistance mechanisms and tolerability issues seen with venetoclax (AbbVie’s ($ABBV) VENCLEXTA). BeOne’s press release framed this as validation of its hematology pipeline following its high-profile rebrand away from the BeiGene name, a move designed to reposition the company’s U.S. commercial identity amid ongoing geopolitical scrutiny of China-linked biotechs.

MCL is a rare and aggressive B-cell lymphoma with limited options after BTK inhibitor failure. The accelerated approval pathway means BeOne will need to confirm clinical benefit in a post-marketing confirmatory trial, but the commercial window is open now. Reuters noted that this positions sonrotoclax directly against the venetoclax franchise, which generated over $2.5 billion in sales last year across indications for AbbVie and its collaboration partner Roche/Genentech.

🧠 BPS Take: The AbbVie/Genentech venetoclax franchise is a $2.5B-plus-per-year business built largely on CLL and some AML sales that has faced no in-class challengers. Venetoclax is an effective drug, but requires a 5-week dose ramp up to minimize the risk of tumor lysis syndrome (TLS). Sonrotoclax has been designed with a much cleaner profile and more refined chemistry. Sonrotoclax landing in MCL first is a smart foot-hold securing move, enabling BeOne to play in an indication where venetoclax has no market presence as they build into the much larger CLL opportunity. Sonrotoclax is already approved in China in both CLL and MCL and BeOne has four Phase 3 studies in CLL ongoing to be used to file in western markets.

Novo Nordisk Drops an "Early Responder" Analysis at ECO. The Real Target? Eli Lilly.

📅 May 12 | 🏢 Novo Nordisk ( ) | 💊 WEGOVY HD (semaglutide 7.2 mg) | 🏷 STEP UP Sub-Analysis (ECO 2026)

Novo Nordisk ($NVO) presented new sub-analyses from the STEP UP trial at the European Congress on Obesity (ECO) in Istanbul this week, highlighting weight loss outcomes with WEGOVY HD (semaglutide 7.2 mg) stratified by speed of initial response.

The STEP UP trial enrolled 1,407 adults with obesity (BMI ≥30, no type 2 diabetes) and ran for 72 weeks, double-blind, with three arms: semaglutide 7.2 mg, semaglutide 2.4 mg, and placebo. The primary results, already published in The Lancet Diabetes & Endocrinology, showed 20.7% mean weight loss on the 7.2 mg dose, 17.5% on 2.4 mg, and 2.4% on placebo.

The new sub-analysis introduced an “early responder” classification: patients who lost 15% or more of body weight by week 24. On the 7.2 mg dose, 26.9% of patients met that threshold and went on to lose 27.7% of body weight at week 72. On 2.4 mg, 20.9% qualified as early responders, losing 24.8% at week 72. Non-early responders on the 7.2 mg dose lost 15.4% on average; non-early responders on 2.4 mg lost 13.2%.

🧠 BPS Take: As a product-positioning tactic, this is a sharp move by Novo. The headline number here is 28% weight loss and fast-onset (15% loss) in roughly a quarter of the patients on high-dose semaglutide. Drawing attention to that high-end number compares favorably to tirzepatide, who at the same conference showed SURMOUNT-MAINTAIN data proving that tirzepatide (ZEPBOUND) at max dose sustains 22.4% weight loss through 112 weeks, and published ATTAIN-MAINTAIN data showing patients can switch from injectable ZEPBOUND to oral FOUNDAYO and keep most of the weight off. Lilly’s is trying to position FOUNDAYO as the long-term weight maintenance option, while Novo is trying to highlight the “rapid weight loss” message, while also trying to subtly strike a favorable efficacy comparison to the average ZEPBOUND patient.

But here is where this may backfire for Novo over the long run. By publishing an early-responder analysis, Novo is implicitly acknowledging that GLP-1 response is not uniform. About 27% of patients are early responders on the high dose. That means roughly 73% are not. Novo is essentially segmenting its own market. Right now, that segmentation works in their favor because 27.7% is a great headline. But what happens when the next wave of competitors enters the obesity space with non-GLP-1 mechanisms? Those companies don't need to beat semaglutide in the full population. They just need to target the 73% of patients who are NOT early responders on semaglutide and offer them something better than 15%.

This is especially relevant given the emerging pharmacogenomics data. A major study published in Nature in April 2026 (23andMe, n=27,885 GLP-1 users) identified a missense variant in the GLP1R gene (rs10305420, Pro7Leu) that significantly predicts weight loss response to semaglutide and tirzepatide. The T allele carriers lost meaningfully more weight (additional ~0.76 kg per allele). They also found that response varies significantly by sex (women respond better, 12.2% vs. 10.0% BMI loss in men), ancestry (European ancestry most responsive), and T2D status (patients with diabetes lose ~2.87 percentage points less). Across all non-genetic factors combined, only about 21% of variance in weight loss was explained. Adding genetics bumped it to 25%. We might be moving moving toward a world where “who responds to GLP-1s” is a genetically answerable question.

And that’s the strategic risk for Novo and Lilly alike. Once you can genotype/phenotype for GLP-1 response, the obesity market stops being a one-size-fits-all blockbuster story and starts looking more like precision oncology, where companion diagnostics and patient selection define clinical and commercial outcomes. The non-GLP-1 pipeline is projected to hit $15.5 billion by 2031 (up from ~$310 million in 2026, per GlobalData). Those later entrants would love nothing more than a companion diagnostic or patient segmentation strategy that identifies the patients who won’t respond well to semaglutide or tirzepatide and routes them toward alternative mechanisms instead.

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🌐 CONNECTING THE DOTS

When the outside world meets biopharma

FDA Commissioner Makary Resigns, Then the Entire Leadership Layer Falls Apart in 72 Hours

📅 May 12-14, 2026 | 🏢 FDA / Policy | 💊 N/A | 🏷 Regulatory Leadership + Industry Response

Marty Makary resigned as FDA Commissioner on May 12, just 13 months into his tenure and on the eve of his Senate Appropriations testimony on the FY2027 FDA budget. The exit was reportedly made under White House pressure after Trump signed off on a plan to oust him, driven in part by Makary’s refusal to approve flavored vapes. Kyle Diamantas, the FDA’s Deputy Commissioner for Food and a JD by training with no medical background, was named acting commissioner. RFK Jr. posted on X that the search for a new commissioner “is already underway.”

But Makary’s exit was just the start. By Friday night, the FDA’s leadership had been gutted across all three critical positions:

Tracy Beth Høeg, acting director of the Center for Drug Evaluation and Research (CDER), was fired on May 15 after she refused to sign a resignation letter.

Høeg was the fifth CDER leader in a single year, following the departures of George Tidmarsh, Richard Pazdur, and others. Michael Davis, CDER’s deputy director, is now acting director.

Katherine Szarama, who had been acting director of the Center for Biologics Evaluation and Research (CBER) for all of 10 days after replacing Vinay Prasad (who himself departed for the second time in April), is also out. Karim Mikhail, former CEO of Amarin who joined FDA last year, is now acting CBER director.

Jim Traficant, FDA chief of staff since last March, was also ousted on Friday.

To summarize the state of affairs: as of this weekend, the FDA has no permanent commissioner, no permanent CDER director, no permanent CBER director, and no chief of staff. All top positions are filled by acting officials operating under a 210-day federal authority limit.

The downstream effects are already visible. Reuters spoke to seven biotech executives, investors, and consultants this week who confirmed that mass FDA layoffs, the revolving door at the commissioner level, and general Trump-era restructuring are pushing smaller biotechs to file Phase 1 INDs in the EU and Australia first. Peter Kolchinsky at RA Capital ($9B AUM) said: “We know that across our companies, the discussions include whether to go ex-U.S. because of recent FDA uncertainty.” One biotech CEO told Reuters their company plans to seek EMA approval to run early-stage oncology trials in three European countries, at roughly $1M in additional filing costs, saying: “The irony of this is it goes against the grain of ‘America First’, because we are offshoring away from the U.S. over to Europe.” Another U.S. biotech opted to run two early-stage trials in Australia this month rather than the U.S. A third said at least two members of their eight-person FDA review team have left, threatening data review timelines.

🧠 BPS Take: Makary’s tenure was a mostly negative bag in my view. He directionally had it right on some things like: utilization of AI, CRL transparency, and speeding up review times, but none of those were ever applied consistently enough to result in more benefit than harm to the sector. Moreover, he really hired some problematic people, who he as a leader did not do a good job reigning in and did an equally job managing-up with his superiors like RFK and Trump.

What is alarming is what happened in the 72 hours after he left. The acting CDER head was fired. The acting CBER head (who had the job for 10 days) is gone. The chief of staff is gone. Apparently the Chief AI officer (which to be honest I didn’t know was a thing at the FDA) is also out.

The person now running the entire FDA is a food lawyer whose prior claim to fame was defending Abbott in an infant formula lawsuit (Abbott lost, paid $495M) and who is a close friend of Donald Trump Jr. A food lawyer running a drug-heavy agency is not a confidence-inspiring signal for anyone waiting on a PDUFA date.

This is just the cherry on top of all the turmoil, capriciousness, and inconsistency this FDA has demonstrated since Trump came into office for a second time. All of that compounds. The agency is operationally diminished at the absolute wrong time, as we fall further behind China in innovating new drugs and testing them in clinical trials. The biotech offshore migration story is the direct, logical consequence. When your fastest path to a Phase 1 readout runs through Melbourne or Amsterdam rather than Rockville, you file there.

I am not confident anyone of meaningful stature, competence, and leadership will take any of these roles. Several big name figures in the Biotech community are petitioning for Rick Pazdur to return. While he would be an experienced and perhaps stabilizing pick, why would anyone want this job if you have to compromise your morals to defend RFK’s ludicrous takes on health and wellness and push through the agenda of any random person who has the president’s ear?

💰 FOLLOW THE MONEY

Deals, dollars, and what they signal

BMS Pays $600M Upfront for $15.2B Hengrui Mega-Pact While $GSK Hands China HBV Launch to Sino Biopharmaceutical

📅 May 11-12, 2026 | 🏢 Bristol Myers Squibb ($BMY) + Hengrui Pharma ($1276.HK) + GSK ($GSK) + Sino Biopharm ($1177.HK) | 💊 13 early-stage oncology/hematology/immunology assets + bepirovirsen | 🏷 Strategic Licensing / Co-Development Alliance + China Commercialization Partnership

Bristol Myers Squibb ($BMY) and Hengrui Pharma ($1276.HK) announced a sweeping bilateral pact on May 12 worth up to $15.2 billion in total milestones. BMS pays $600 million upfront, plus $175 million on each of the first two anniversaries, to secure ex-China rights to four Hengrui oncology and hematology assets and joint discovery rights on five additional programs. Hengrui receives Greater China rights (mainland China, Hong Kong, Macau) to four BMS immunology assets and will lead early human development in that region. The transaction is expected to close in Q3 2026.

BMS CFO David Elkins had publicly flagged at a Citi event that China’s early-stage development speed is a competitive advantage, citing McKinsey data showing Chinese sponsors run proof-of-concept trials 50 to 70 percent faster than Western peers. This deal arrives roughly a year after Hengrui’s $12 billion licensing agreement with GSK, cementing Hengrui’s status as the most sought-after Chinese R&D partner in the industry right now.

One day earlier, on May 11, GSK ($GSK) moved in a different direction with China exposure by announcing an exclusive collaboration with SBP Group, the hepatology-focused unit of Sino Biopharmaceutical ($1177.HK), to support the China launch of bepirovirsen, a potential first-in-class antisense oligonucleotide for chronic hepatitis B. Under the 5.5-year supply arrangement, CTTQ purchases the drug from GSK while GSK retains all revenue recognition.

🧠 BPS Take: Two deals, two flavors of the same strategic logic: Western pharma cannot ignore China’s patient populations or its R&D throughput, regardless of geopolitical headwinds. I find the BMS/Hengrui structure particularly interesting because it is almost a trade of sorts. BMS buys into part of a Chinese pipeline, but it is also licensing its own immunology assets back into China through a local partner who will run early development there. That is a mature, cost-conscious way to keep China exposure without building out your own local clinical infrastructure. The $600 million upfront is real money on undisclosed early-stage assets, which tells you how seriously BMS is treating its post-REVLIMID pipeline rebuild. I am curious to see what targets and modalities end up coming out of Hengrui for this deal.

The GSK/Sino bepirovirsen deal is structurally simpler but strategically smart. GSK is not giving up economics; it is essentially buying a distribution army in a foreign market. If bepirovirsen clears China’s NMPA and delivers even modest functional cure rates, that 5.5-year supply pact becomes very valuable very fast.

I’ll also be watching whether these deals attract scrutiny under the BIOSECURE Act or successor legislation. Also watching how Hengrui’s stock responds over the next month, because if this gets blocked or renegotiated, the ripple effects for the entire wave of China in-licensing deals will be significant.

Isomorphic Labs Pulls In $2.1B Series B, Becoming the Largest Single Bet on AI Drug Discovery

📅 May 12, 2026 | 🏢 Isomorphic Labs (subsidiary of Alphabet, $GOOGL) | 💊 AlphaFold-derived AI drug design platform | 🏷 Mega Series B Financing

Isomorphic Labs, the DeepMind spinout founded by Demis Hassabis, closed a $2.1 billion Series B led by Thrive Capital, with participation from new investors MGX (the Abu Dhabi state-linked technology fund), Temasek, and CapitalG, alongside existing backers Alphabet ($GOOGL) and GV. BioSpace reports this is the second-largest biotech financing round ever recorded. Proceeds will fund expansion of the company’s generative drug-design models built on top of AlphaFold’s structural biology foundation.

Isomorphic has been operating largely in stealth on its own internal pipeline while licensing its platform capabilities to partners including Eli Lilly and Novartis. The fresh capital is expected to accelerate moving those computational designs into wet-lab validation and, eventually, clinical programs. Forbes describes the round as “the biggest bet yet on AI drug discovery,” framing the fundraise against a broader investor thesis that generative AI will compress preclinical timelines by years, not months.

🧠 BPS Take: $2.1 billion for a company with no approved drug and no disclosed Phase 1 data is a remarkable statement of faith in a platform. The investors backing Isomorphic Labs are overwhelmingly tech-first investors and mega-funds, rather than biotech VCs. While the headlines are biotech/drug development focused, Isomorphic is really being priced like a Tech/AI company and not a drug developer. Isomorphic is building upon AlphaFold’s protein prediction capabilities to also modeling potential druggable sites on the target and using AI to create several “keys” that fit into those binding pockets. Ultimately, these still need to tested in animals and then humans, but their platform can conceivably cut out a lot of the fat of generating drug leads in a program. The proof will be in the pudding, and IsoMorphic, with Google’s backing is partnered with multiple Big Pharmas on drug discovery collaborations. Let’s keep an eye on timelines to IND here and how quickly IsoMorphic is able to progress their own programs. As we’ve seen with other AI drug discovery companies, like Recursion, these tech-first companies can raise huge rounds, sign multiple big collabs, and get a several year grace period where they crank out several “cool” drug candidates before the pressure of actually getting drugs to work in the clinic sets in.

Create Medicines Raises $122M Series B to Bring RNA-Based In Vivo CAR-T Into the Clinic

📅 May 14, 2026 | 🏢 Create Medicines (private) | 💊 In vivo CAR-T platform (autoimmune + oncology) | 🏷 Series B Financing

Create Medicines, a Massachusetts-based biotech developing RNA-based in vivo CAR-T therapies, announced a $122 million Series B led by Newpath Partners, with ARCH Venture Partners and Hatteras Venture Partners joining the round. The company’s platform is designed to engineer CAR-T cells directly inside the patient’s body using RNA delivery, bypassing the costly and logistically complex ex vivo manufacturing process that currently limits conventional CAR-T to a small number of academic medical centers.

The round positions Create in the same rapidly consolidating in vivo CAR-T subspace as Lilly’s $7 billion acquisition of Kelonia earlier this year and the AbbVie ($ABBV) partnership with Capstan Therapeutics. STAT News notes that Create’s autoimmune disease focus mirrors where conventional ex vivo CAR-T has already shown dramatic early results, with the in vivo approach offering the potential to reach far more patients if manufacturing hurdles can be eliminated. Proceeds will fund IND-enabling studies and the company’s first clinical programs.

🧠 BPS Take: The in vivo CAR-T space is moving faster than almost any other subfield in cell and gene therapy right now. Create’s $122 million round is well-sized as it is one of the few in vivo companies with clinical data (in solid tumors to boot). From their corporate presentation, it appears they have a broad set of cell and antigen targeting technologies across oncology and autoimmune disease. Given the high density of players in this space, speaking to and proving differentiation in your vector’s targeting capabilities vs. competitors will be important, and Create does a good job explaining where they may be better than their peers. In solid tumors, they’ve already shown one partial response with a TROP2 CAR-myeloid cell program. It appears their approach in solid tumors is also guided at in vivo delivery into multiple cell types at once (NKs, Myeloids, T-cells, etc.) which is somewhat unique to them. More robust clinical data across all these programs will be the true test, but it is good to see companies speak to aggressively speak to differentiation against competitors early on. Create is definitely one to follow as we head into conference season, and given the penchant for Big Pharmas to acquire in vivo Cell Therapy companies early-on in their company life cycle, perhapsLet’s do a remixed version of this image. Make it “Week of May 11.” Also, only include logos for FDA, Novo Nordisk, and Bristol-Myers Squibb. they won’t be around for long.

Back next week with more BioPharma strategy takes! Share this with a friend or colleague if you found it helpful.

Of all the types of cancers, blood cancers have perhaps seen the most meaningful therapeutic advances. People often joke that blood cancers are the “the good cancers”, since a large chunk of them are quite curable or manageable long-term. Chronic Myeloid Leukemia (CML) patients have normal life expectancy because of the advent of tyrosine kinase inhibitors like GLEEVEC. Chronic Lymphocytic Leukemia (CLL) is well managed with BTK inhibitors. Acute Lymphoblastic Leukemia (ALL) and pretty much all types of B-cell lymphomas are curable with chemo-immunotherapy or CD19-based CAR-T therapy. Multiple Myeloma has steadily seen increases in overall survival with discovery of novel targets, new modalities (CAR-T and T-cell engagers) and multi-drug regimens, so much so that many leading key opinion leaders feel myeloma is entering its chronic disease era.

It has truly been one of the most optimistic areas of cancer research. I think that is why everyone really loves going to the annual American Society of Hematology (ASH) meeting every year. You’ll regularly see new data from novel MOAs that have response rates in the 90’s and complete response rates in the 70s and 80s.

That certainly isn’t the case for every hematologic malignancy. Drug-knowers will realize I omitted some pretty meaningful diseases from that list, notably acute myeloid leukemia (AML) and myelofibrosis (MF), which the rest of this post is about. Not every cancer your blood can get has yet to benefit from the major advancements our field has been able to materialize in advanced therapeutics.

But it has to be coming soon right? It must just be market forces that haven’t trickled their way down to the smaller blood cancers yet. Lymphomas and myelomas are sizable competitive markets, but those same step-change innovations we brought forth should certainly find their footing in MF, right? After all, Lilly (of all companies) just bought a company developing an MF drug for up to $2.3B

The Prolonged JAKAFI Era

Early on in my BioPharma career, I spent a great amount of my time focused on blood cancers, of which myelofibrosis (MF) was one of them. Back when I was covering this space, there was only one game in town - JAKAFI. JAKAFI is Incyte and Novartis’ JAK inhibitor which truly revolutionized treatment for MF. Before its arrival in 2011, treatment was largely reactive and palliative, relying on non-specific agents like hydroxyurea that often failed to address the core symptoms of the disease. It provided the first consistent way to significantly reduce massive splenomegaly (enlarged spleen) and debilitating constitutional symptoms like night sweats, bone pain, and extreme fatigue, which drastically improved patients' quality of life. But more importantly, it was the first to show an overall survival benefit.

As is the case with so many markets in BioPharma, a new idea doesn’t often get pursued in a vacuum. Other players (Gilead included) looked to advance slightly more refined version of JAK1/2 inhibitors to improve on JAKAFI’s profile.

However, it took almost 8 years for new JAK inhibitor to make it to market. While JAKAFI displayed great symptom resolution (TSS) and spleen reduction (SVR), it tended to cause very high rates of anemia, which would often require patients to get blood transfusions. Treatment with next-gen JAK inhibitors from competitors shifted towards moderating SVR to spare red blood cells and reduce the blood transfusion requirements. Now there are four JAK inhibitors approved (all the ones you see in the table above) all with their particular niche in the market place.

Despite all this competition, JAKAFI still reigns supreme, but is facing a growing threat from OJJAARA, which has quickly become the go-to treatment for patients with anemia. This is a classic case of first-mover advantage paying off. JAKAFI has had significantly more time on market than its competitors, more physician experience with its product, the most robust survival data, and the benefit of still being the preferred medicine in treatment guidelines, and also the preferred treatment on formularies. But trouble may be on the horizon. Generic ruxolitinib entry is now estimated as early as December 2028, and Incyte has already faced patent litigation from generic challengers. The extended-release formulation approval is one defensive move, but whether it drives meaningful patient switching before generics arrive is an open question.

All that being said, when I put together the MF landscape for this post, I was surprised to see that the entire approved treatment portfolio is still just varieties of JAK inhibitors.

Too soon to subscribe? I have an idea.

The Late-Stage MF Graveyard

However, it’s not like other strategies weren’t tried. MF’s history has some recent failures in its memory:

• PI3K-delta inhibitors: This class was studied in combination with JAKAFI to enhance response. JAK inhibitors are great at reducing symptoms and shrinking the spleen, but do not slow or reverse marrow fibrosis or offer a path to cure. Incyte had its own program in this vein (parsaclisib), but it’s pivotal study was stopped early due to the added benefit over JAKAFI alone being too small to justify the added risk of thrombocytopenia.

• Luspatercept (activin receptor ligand trap): Also known as REBLOZYL, this drug was aimed at reducing transfusion dependence. Unlike in MDS where it has proved to be successful, luspatercept failed to a show an improvement in this metric in MF patients.

• Apoptosis pathways: Along the same vein as PI3K-delta, companies looked to target the p53 apoptotic pathway via MDM2 and BCL-2 inhibitors to add to JAK1/2 inhibition efficacy. AbbVie pushed all the wya into two Phase 3 studies with navitoclax (BCL-2 inh) but ultimately scrapped development in MF after one of its studies was unable to show a benefit in TSS, despite a significant benefit in SVR. Kartos and Novartis each advanced their own respective MDM2 inhibitors. Novartis ended up deprioritizing it’s asset, while Kartos’ navtemadlin continues on in a P3 study in 1L MF after mixed results in a P3 study in 2L+ MF.

• Other approaches: A couple more that have had disappointing results: Hedgehog inhibitors, most notably Pfizer’s glasdegib, was terminated due to lack of efficacy and GI toxicity issues. Novartis tried an anti-TIM3 antibody, pursuing an immuno-oncology approach to myelofibrosis, but that was also terminated due to lack of efficacy.

Common theme across these tried-and-failed approaches is toxicity issues in combination with JAKAFI, commonly myelosuppression. The bar for success is unusually high in myelofibrosis as well. JAKAFI was approved showing improvements in total symptom score and spleen volume reduction. Many of the failures in this space have been able to show spleen volume reduction, but have failed to show a significant improvement in symptoms. While the combinatory drugs are helping to kill malignant cells more effectively, they come with additional adverse events canceling out the symptomatic relief patients feel.

More mechanistically, prolonged use of JAKAFI and other JAK inhibitors can downstream lead to mutations that render the baseline JAK backbone ineffective. The JAK problem is hard to avoid, just given how central the JAK-STAT pathway is to the pathology of myelofibrosis. However, thinking has shifted on what the appropriate endpoints for novel therapies in this space should be. The field is moving away from the “spleen-centric” era where SVR and TSS were essentially surrogate measures of efficacy; now the next wave of novel therapies are focused on showing hard outcomes like overall survival, demonstrating bone marrow fibrosis reduction (BMF grading), and reduced burden of mutant clones (Variant Allele Frequency, VAF). This offers some newfound hope to a new set of therapeutic strategies being pursued in early/mid-stage clinical development.

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So Where is the Field Headed?

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Welcome back to Last Week Tonight in BioPharma (LWTB). What a week!

This week, Cytokinetics hit it big non-obstructive hypertrophic cardiomyopathy setting up strategic crossroads, FDA instability crops up once again with Marty Makary likely to be fired by Trump, and Roche takes a major step in AI.

All that and more below. Let’s get into it!

But before that….Happy Mother’s Day to all moms, grandmothers, and mother figures reading this! This day always brings my mind back to women’s health. Both how far we’ve come and how far we still have to go.

Over the last five years we’ve delivered several new treatments in women’s health (outside of oncology): Zurzuvae (2023), the first oral postpartum-depression treatment; Veozah (2023), the first non-hormonal hot-flash therapy; and Orilissa and Myfembree, the first new oral endometriosis drugs in over a decade. Women’s health VC funding hit a record $2.6 billion in 2024, up 50% year-over-year.

Yet despite these new advances, it is so clear we still have a long way to go. Endometriosis affects ~190 million women, takes nearly seven years to diagnose, and has no disease-modifying therapy. PCOS, the most common endocrine disorder in reproductive-age women, has zero FDA-approved treatments. There are several studies ongoing studying GLP-1s in this space, with hopefully positive data forthcoming. Uterine fibroids affect up to 80% of women by age 50 and up to 90% of Black women, yet for decades the default “treatment” was hysterectomy. Preeclampsia causes over 70,000 maternal and 500,000 fetal deaths annually, with the only treatment being delivery. Black women in the U.S. die from pregnancy-related causes at 3.5× the rate of white women. Two-thirds of Alzheimer’s patients are women. 80% of autoimmune-disease patients are women. Yet only ~6% of private healthcare capital targets women’s conditions.

We've made progress, but we're nowhere near where we need to be. Women's health is human health. Our industry has the the tools, obligation, and and alignment with financial interests to make even more progress over the next five years.

Now onto an interesting week in BioPharma.

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📡 PRESS RELEASE DECODER

What the press releases actually mean

Cytokinetics’ Aficamten Hits Both Endpoints in nHCM — First Positive Phase 3 in a Population With Zero Approved Therapies

📅 May 5 | 🏢 Cytokinetics ( ) | 💊 Aficamten (MYQORZO) | 🏷 Phase 3 Topline Data

Cytokinetics reported positive topline results from ACACIA-HCM, the pivotal Phase 3 trial of aficamten in symptomatic non-obstructive hypertrophic cardiomyopathy (nHCM). The trial randomized 516 patients 1:1 and met both dual primary endpoints at Week 36: KCCQ-CSS improved by 3.0 points over placebo (95% CI 0.5–5.5, p=0.021), and peak VO2 improved by 0.67 mL/kg/min over placebo (95% CI 0.22–1.1, p=0.003). All key secondary endpoints also hit with high significance (p<0.001), including NYHA functional class improvement, composite exercise parameters, and NT-proBNP reduction.

Safety was consistent with the known cardiac myosin inhibitor profile. LVEF fell below 50% in 10% of aficamten patients versus 1% on placebo. Two patients on aficamten had serious adverse events of heart failure associated with low LVEF. Dose interruptions for LVEF <40% occurred in 3% of aficamten-treated patients. Completion rates were comparable between arms (88.4% vs 90.3%).

This is aficamten’s second Phase 3 win — the first was SEQUOIA-HCM in obstructive HCM, which supported the FDA approval of aficamten as MYQORZO for symptomatic oHCM (already approved in the U.S., EU, and China). Cytokinetics has signaled it will file a second sNDA for the nHCM indication based on ACACIA-HCM data. Full results are expected at an upcoming medical congress.

🧠 BPS Take: This is a genuinely important clinical result. The nHCM population, which represents roughly half the HCM population, has had no approved disease-modifying therapy. Cardiologists have had nothing to offer except symptom management and the assumption that without obstruction, the disease was pharmacologically harder to treat. ACACIA-HCM changes that completely.

Strategically, this puts Cytokinetics in a position BMS cannot match. If the nHCM sNDA converts to approval, aficamten becomes the only cardiac myosin inhibitor labeled for both obstructive and non-obstructive HCM, giving CYTK commercial opportunity across the full spectrum of HCM. Remember, BMS’ Camzyos (mavacamten) failed in the P3 ODYSSEY-HCM study, leaving this opening for CYTK to be first-to-market in nHCM. BMS is working on a new study to tackle nHCM with CAMZYOS, but they will undoubtedly be later to market, after spending $13B to acquire mavcamten from MyoKardia in 2020.

The question I keep coming back to: does a second Phase 3 win in the same disease space accelerate acquisition interest, or does Cytokinetics now have enough standalone value to stay independent? CYTK was a name I called out on my buyout list earlier in the year. They are sitting at just under $10B in market with a product that may get low single-digit billions in revenue. The BMS precedent of $13B may be where some acquirers anchor too, but CYTK may be able to garner more given their competitive edge. CYTK could make sense for a strong CV player like Novartis or AstraZeneca. Watch the BD chatter closely over the coming months.

FDA Agrees to Reconsider Ebvallo CRL — Pierre Fabre Gets a Path Forward After a Rejection That Didn’t Add Up

📅 May 7 | 🏢 Pierre Fabre / Atara Biotherapeutics ( ) | 💊 Ebvallo (tabelecleucel) | 🏷 FDA Type A Meeting / Regulatory Update

Pierre Fabre announced that the FDA has completed a Type A meeting on the Complete Response Letter (CRL) issued in January 2026 for tabelecleucel, an allogeneic, off-the-shelf EBV-specific T-cell immunotherapy for EBV-positive post-transplant lymphoproliferative disease (EBV+ PTLD). The meeting outcome provides a resubmission path — Pierre Fabre described the discussion as reaching an accord on the BLA path forward. Type A meetings are reserved for urgent matters, including disputes over CRL decisions, and the FDA’s willingness to engage at this level signals meaningful internal reconsideration.

Tabelecleucel targets an ultra-rare, frequently fatal malignancy in immunocompromised post-transplant patients who have failed rituximab. Unlike autologous cell therapies, it doesn’t require patient-specific manufacturing — a critical advantage in a population often too ill to wait for custom products. The original CRL was widely described as inconsistent with prior FDA guidance the agency had provided to the sponsor during development.

🧠 BPS Take: The FDA walking back a CRL like this is not normal, and continues along a pattern of FDA capriciousness we have seen under this administration. Type A meetings exist for urgent disputes, but the agency providing a clear resubmission path on a rejection that both the company and external observers described as contradicting prior guidance is genuinely odd.

This story matters on two levels. First, tabelecleucel is a an allogeneic, off-the-shelf EBV-specific T-cells for critically ill transplant patients with almost no alternatives. The original CRL was always hard to reconcile with the clinical and regulatory logic of the program.

Second, and more troubling, the same week Sanofi pulls Tzield from a priority review program citing political appointee interference, we have the FDA providing a resubmission path on a rejection that didn’t track with its own prior guidance. Pair that with other controversial decisions we’ve seen this year (e.g. Replimune, UniQure, Sarepta, etc.) and you have one of the most important regulatory agencies on shaky ground. More on this in Connecting the Dots.

Incyte Gets Jakafi XR Approved — Lifecycle Management Play With a Tight Window Before the Patent Cliff

📅 May 1 | 🏢 Incyte ( ) | 💊 Jakafi XR (ruxolitinib extended-release) | 🏷 FDA Approval

The FDA approved Jakafi XR, a once-daily extended-release formulation of ruxolitinib, across all three approved indications: myelofibrosis (MF), polycythemia vera (PV), and graft-versus-host disease (GVHD). The existing twice-daily Jakafi remains on the market. The XR formulation is designed to maintain therapeutic exposure over a 24-hour dosing interval, with the rationale that once-daily dosing improves adherence in a chronic disease population.

Jakafi is Incyte’s largest commercial asset. In Q1 2026, Jakafi generated $758 million in U.S. net sales — annualizing to roughly $3 billion. The drug’s core patents are expected to expire around 2027-2028, creating significant near-term generic exposure. The MF treatment landscape has grown more competitive since Jakafi’s original approval: pacritinib, fedratinib, and momelotinib are all FDA-approved alternatives with differentiated profiles in specific subpopulations.

🧠 BPS Take: This is one of the purest forms of lifecycle management. I don’t say that dismissively. This is what brands close to the end of their exclusivity do. Spin up an extended release formulation or a new route of administration. That new offering has its own patent life that can extend beyond the LOE of the original formulation. Incyte’s bread and butter is Jakafi and its staring at an estimated 2028 patent cliff on a ~$5B product (including Novartis’ share of revenues).

Once-daily dosing is a tangible convenience benefit compared to immediate release (twice-daily) Jakafi, but brings it to parity with most of the other JAK inhibitors in the myelofibrosis and polycythemia vera space. The push here will come from the Jakafi commercial teams aiming to influence patient and docs to switch to the XR formulation over the two year window prior to Jakafi IR coming off patent. Incyte tried to give themselves more runway for this, but ran into regulatory issues during their first attempt at an XR formulation back in 2023. Payers may not automatically cover Jakafi XR over generic ruxolitinib once generics hit the market, unless they are getting a big discount on the back end.

I think the bigger question for me is why is everything in MF still a JAK inhibitor? Aside from the other JAK inhibitors that have been approved in this space, this XR formulation is the last major innovation the MF landscape has seen. I am digging into this curiosity in a forthcoming post for paid subscribers, so stay tuned.

🌐 CONNECTING THE DOTS

When the outside world meets biopharma

The FDA is Coming Apart — Makary Firing, Flavored Vapes, RFK’s SSRI Push, and What It Means for Drug Development

📅 May 4–8, 2026 | 🏢 POLICY/MACRO | 🏷 FDA Credibility Crisis

Monday, May 4: HHS Secretary Robert F. Kennedy Jr. announces the “MAHA Action Plan” at a Mental Health and Overmedicalization Summit, announcing federal initiatives to reduce SSRI antidepressant prescribing. The plan includes new Medicare/Medicaid reimbursement for clinicians who help patients taper off psychiatric medications, prescribing trend transparency, and provider training. Kennedy’s statement: “Psychiatric medications have a role in care, but we will no longer treat them as the default.” Kennedy has previously, without evidence, linked SSRIs to mass shootings and claimed withdrawal symptoms are worse than heroin.

Tuesday, May 5: The Wall Street Journal reports Trump directly pressured FDA Commissioner Makary to approve flavored e-cigarettes. Makary had been blocking authorization since a February memo indicated he needed more time to evaluate the science. The same day, Sanofi requests removal of Tzield from the FDA’s Commissioner’s National Priority Voucher (CNPV) program after CDER head Dr. Tracy Beth Høeg became directly involved in the review.

Wednesday, May 6: The FDA announces its first-ever authorization of fruit-flavored e-cigarettes — four products from a company called Glas with Bluetooth age-verification technology. The timing, coming immediately after Trump’s pressure became public, is impossible to ignore. Public health groups and a bipartisan group of senators (Durbin and Collins) criticize the decision.

Thursday, May 7: New York Post runs “Knives out for FDA head Marty Makary.” NBC reports Trump is considering firing him. The frustrations are multiple and overlapping: slow-walking flavored vape approvals, failure to release a promised mifepristone safety review before midterms (Bloomberg reported in December that Makary told officials to delay it), the UniQure Huntington’s gene therapy rejection that led to Vinay Prasad’s second ouster, and the Moderna mRNA flu vaccine application refusal that was reversed days later.

Friday, May 8: Two stories break simultaneously. CNN reports Trump has “signed off” on a plan to oust Makary, according to a senior administration official, though no formal dismissal has occurred and Trump told reporters “I’ve been reading about it, but I know nothing about it.” Separately, Reuters reports exclusively that Kennedy’s HHS officials explored whether they could ban specific SSRIs — including Zoloft, Prozac, and Lexapro — as Kennedy prepared his MAHA plan. HHS denies the report. Regulatory experts are uniform: the FDA cannot unilaterally ban approved medications without new safety evidence. The American Psychiatric Association considers SSRIs a first-line, evidence-based treatment for depression and “strongly objects to framing the nation’s mental health crisis as primarily a problem of ‘overmedicalization.’”

🧠 BPS Take: If you've been a regular BPS reader you won't be surprised by this volatile behavior from the FDA, but this week felt like it reached a new level. Three threads connect.

First, Makary blocked flavored vapes in February based on a scientific review he said needed more time, Trump pressured him directly, and the FDA reversed course within days of that pressure becoming public. Whether or not the flavored vape authorization is scientifically defensible, it sure feels like a science-based decision was reversed under direct presidential pressure, and that is not how the FDA is supposed to work. Yet another example of why we should consider making it a more independent body, like the Fed.

Second, Kennedy's HHS exploring an actual ban on specific approved SSRIs threatens to set a dangerous precedent if it happens. These are drugs backed by decades of clinical evidence and considered first-line treatment by every major psychiatric organization. There is an argument to be made for combatting overprescription, but an outright ban would likely do more harm than good. The FDA doesn't have the legal authority to unilaterally ban approved drugs without new safety evidence, and this would require formal safety review processes that take months or years, but the signal this exploration sends to the industry, that approved drugs could be targets of political campaigns, is profoundly destabilizing.

Third, CNN reports Trump has signed off on ousting Makary but hasn't formally acted, in part because there's no replacement lined up. There are already so many holes in the FDA after so much staff turnover, and if Makary goes, that's another major destabilizer to an already chaotic agency. It's not like we've seen a deep bench of competent operators in this administration either, and I am not too confident that whoever takes over will exceed an already low bar.

The through-line across all three is an FDA that has operated inconsistently in the face of direct political pressure from higher-ups, and the unpredictability at the review level is emblematic of that. When Sanofi exits a priority review program because a political appointee intervened in a way the company couldn't predict, when the Ebvallo CRL contradicts prior guidance, when Moderna's flu vaccine application gets rejected then un-rejected within days, and when the Commissioner himself may be fired for not approving consumer products fast enough, the review process itself stops being rule-governed.

BioNTech Cuts 1,860 Jobs and Closes Four Manufacturing Sites

📅 May 5 | 🏢 BioNTech ( ) | 🏷 Restructuring / Workforce Reduction

BioNTech announced the elimination of approximately 1,860 manufacturing positions — roughly 25% of its global workforce — and the closure of four facilities: Idar-Oberstein, Marburg, and Tübingen in Germany (closing by end of 2027) and a Singapore site (closing during 2026). All four were scaled up during the pandemic for mRNA vaccine production. BioNTech’s COVID vaccine revenues peaked at approximately €19 billion in 2021. The company is funding an oncology pipeline pivot on depleting reserves, with lead mRNA cancer vaccine programs BNT111 (melanoma) and BNT116 (lung cancer) in Phase 2 — neither generating revenue.

🧠 BPS Take: BioNTech rose to prominence on the back of its COVID-19 vaccine business. As has been the case for other COVID-19 drug makers in that space, sales have been on a steady fall. Declining demand warrants pairing back capital expenditures for that business segment.

BioNTech was always an Oncology company at its core. Modality agnostic and Oncology focused. They’ve built an impressive pipeline in that therapeutic area, spanning bispecific antibodies, mRNA vaccines, ADCs, and other modalities. COVID-19 always felt like they were in the right place at the right time. While layoffs and site closure are never smooth, this is probably the right long-term moved (despite the short-term pain) to reallocate resources towards its oncology business.

What I am curious about is who will take over the helm of this company and guide it during this new chapter, while all this restructuring is in the works? The founders are stepping out to run a new spinout and it feels like this should be quite an attractive job opportunity for an outsider. I’m sure the board has no shortage of interested candidates. BioNTech is set up well to be a pure play oncology growth story. It has multiple late-stage studies across a diversified set of assets with rather large market opportunities and is well capitalized to invest in its own commercial future and invest in novel early-stage bets.

💰 FOLLOW THE MONEY

Deals, dollars, and what they signal

Bayer Acquires Perfuse Therapeutics for Up to $2.45B — First Drug Deal in Years Targets the Glaucoma Adherence Problem

📅 May 6 | 🏢 Bayer ($BAYN.DE) / Perfuse Therapeutics (Private) | 💊 PER-001 (intravitreal implant) | 🏷 M&A — Acquisition

Bayer will acquire Perfuse for $300 million upfront and up to $2.15B in milestones. The deal’s centerpiece is PER-001, an intravitreal implant currently in Phase 2 for glaucoma and diabetic retinopathy. The implant blocks a protein that constricts blood vessels and contributes to ocular damage — a mechanistically distinct approach from existing treatments. In glaucoma, it’s being studied as a way to improve vision; in diabetic retinopathy, it targets retinal blood flow restriction. Perfuse reported positive Phase 2 data in both indications last year. This is Bayer’s first major drug company acquisition since 2021.

🧠 BPS Take: Bayer has been in need of something to revitalize the prospects of its drug business. They’ve been in restructuring mode under CEO Bill Anderson since his arrival, the pharma pipeline has been visibly thin, and Eylea’s biosimilar exposure was always going to require a pipeline answer. The deal structure is fairly sensible for Bayer. This sort of backloaded deal probably works out better for them given how much debt they are saddled with and litigation payment obligations. This doesn’t solve all their problems, but is a step in the right direction. Hopefully one day in the future they will take their medicine and break up their disparate businesses into separate entities.

Roche Acquires PathAI for Up to $1.05B — The Most Strategically Coherent AI-Pharma Deal This Year

📅 May 7 | 🏢 Roche ( $ROG.SW ) / PathAI (Private) | 💊 AI digital pathology platform | 🏷 M&A — Acquisition

Roche will pay $750 million upfront with up to $300 million in milestones for PathAI, an AI-powered digital pathology company. PathAI’s platform applies machine learning to analyze pathology slides for cancer diagnosis, biomarker identification, and companion diagnostic development. PathAI had raised approximately $255 million in venture funding. The acquisition positions Roche to integrate AI-driven pathology directly into its $16 billion diagnostics business (Roche Diagnostics, Ventana).

🧠 BPS Take: This is one of the most strategically coherent AI-pharma deals I’ve seen. Roche can integrate PathAI into a $16B diagnostics business that already sits at the intersection of oncology, companion diagnostics, and drug development. They are getting a data flywheel: every pathology slide processed through PathAI’s algorithm improves the model, which improves diagnostic accuracy, which improves clinical trial patient selection, which improves drug approval rates. Overtime this starts to look like a competitive moat that gets harder to replicate with every slide processed.

In oncology you sort of have two paths to success. Go broad or go narrow. Go broad is a lot harder to do, requires some luck, but in the end you can end up with a drug like Keytruda that is approved in nearly every solid tumor, or even Rituxan, which blanketed all of B-cell malignancies in its heyday. Narrow requires precision. This is your classic companion diagnostic or biomarker driven treatment strategy. Find the sub-segment that your drug really responds to and carve out a strategically advantageous position in that sub-segment. Revolution Medicines is doing this to great effect right now in mKRASG12 pancreatic cancer, but we have so many examples of building strong businesses with this strategy (ALK, EGFR, HER2, BRCA, etc.), and this PathAI deal seems like it will better equip Roche to take advantage of that.

GSK Licenses ALK7-Targeting siRNA from China’s SiranBio in Up to $1B Cardiometabolic Deal

📅 May 6 | 🏢 GSK ( ) / SiranBio (Private, China) | 💊 SA030 (siRNA targeting ALK7) | 🏷 Licensing Agreement

GSK licensed global rights to SA030, an siRNA therapeutic targeting ALK7 (activin receptor-like kinase 7) for visceral fat reduction and cardiometabolic disease, from China-based SiranBio. Deal terms: $55 million upfront, up to $1 billion in milestones. SA030 is in Phase 1 with no public efficacy data. ALK7 inhibition has been shown preclinically to selectively reduce visceral adipose tissue — the metabolically harmful fat depot associated with cardiovascular disease, insulin resistance, and type 2 diabetes.

🧠 BPS Take: GSK’s cardiometabolic strategy is about being complementary to GLP-1s. Unlike their peers rushing to find the me-three/four GLP-1 to bring to market, GSK is telling you that they’re not interested in that. They’d rather be a combinatory partner to a GLP-1 backbone to enhance specific treatment effects. This ALK7 asset aims to more heavily target visceral fat, which a lot of science points to as one of the primary drivers of metabolic dysfunction. GLP-1s already help reduce visceral fat to a good degree, but perhaps adding ALK7 inhibition can further that. Notably there are still patients who don’t respond to GLP-1s or respond sub-optimally, and this sort MOA that works more on the thermogenesis and adipocyte targeting axis could be an effective alternative.

Back next week with more BioPharma strategy takes! Share this with a friend of colleague if you found it helpful.

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Welcome back to Last Week Tonight in BioPharma (LWTB). What a week! I had a hard time pairing this one down given all the interesting activity we saw. Many deals, data readouts, and strategic updates left on the cutting room floor.

This week, Sun Pharma dropped $11.75B on Organon in a rare India ➡️ US deal, AstraZeneca had a split ODAC day, and Intellia lands the first in vivo gene editing drug to register a positive Phase 3 readout but no one told the stock price. Meanwhile, the FDA is running fast to make real-time clinical trials standard practice, Lilly continues its deal spree, and IPO markets are looking healthy again.

All that and more below. Let’s get into it!

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For instance, this week I wrote an essay about prediction markets for clinical trial outcomes, comparing them to sports betting markets to learn about their limitations, and discuss why these types of markets are likely to be a net negative for drug makers and patients.

If you’re not ready to commit to being a paid subscriber, but still want to support my work, you can always show your appreciation by buying me drink 😉

Cheers 🥂!

📡 PRESS RELEASE DECODER

What the press releases actually mean

AstraZeneca’s Split ODAC Day — Camizestrant 6-3 Against, Truqap 7-1 In Favor

📅 Date: 2026-04-30 | 🏢 Company: AstraZeneca ( ) | 💊 Drug/Asset: Camizestrant (SERD), Truqap (capivasertib, AKT inhibitor) | 🏷 Event Type: FDA ODAC Votes

AstraZeneca faced two ODAC votes on the same day (the committee’s first meeting in nine months) and walked away with a split decision. In the morning session, ODAC voted 6-3 against the benefit-risk profile of camizestrant, an oral SERD, for HR+/HER2- metastatic breast cancer. In the afternoon, the same committee voted 7-1 (one abstention) in favor of Truqap (capivasertib) plus abiraterone and prednisone for PTEN-deficient metastatic hormone-sensitive prostate cancer.

The camizestrant rejection wasn’t a straightforward efficacy dispute, it was a rejection of AstraZeneca’s entire proposed treatment paradigm. The SERENA-6 trial used circulating tumor DNA (ctDNA) monitoring to detect ESR1 mutations while patients were still responding to first-line therapy (aromatase inhibitor + CDK4/6 inhibitor), then switched them to camizestrant before radiographic disease progression. The trial showed a 56% PFS improvement, median 16.0 months vs. 9.2 months for patients who stayed on the aromatase inhibitor. But OS data were immature with no benefit signal, the control arm didn’t allow crossover to camizestrant, and only 14% of control patients received any oral SERD in subsequent treatment.

The FDA’s core objection was that the trial doesn’t answer whether switching early is better than switching at progression. As FDA reviewer Mirat Shah put it, “the biggest concern is that approving camizestrant would include the endorsement of a treatment paradigm that does not have established clinical benefit.” The agency also flagged the precedent risk, that biomarker-guided early switching could proliferate across tumor types without evidence it actually extends lives. Multiple ODAC members agreed that ESR1 mutation detection hasn’t been proven as a predictive biomarker (indicating treatment will help) vs. merely a prognostic one (indicating disease is worsening regardless). The patient representative was the most direct: “I really wonder if we are again exploiting the hope of women with metastatic breast cancer that somehow, if they’d known earlier, the trajectory of the disease would be different.”

The Truqap vote was more straightforward. CAPItello-281 showed radiographic PFS of 33.2 months vs. 25.7 months (HR 0.81) with capivasertib added to abiraterone in PTEN-deficient metastatic hormone-sensitive prostate cancer. OS was immature (HR 0.90, not significant). FDA flagged toxicity concerns like hyperglycemia, rash, discontinuations, and deaths, and questioned whether the ~7.5-month PFS gain justified the added burden in an early, minimally symptomatic population. But the panel concluded that the unmet need in PTEN-deficient disease and evidence of target engagement were sufficient, with physicians expected to exercise discretion in patient selection. The single no-vote (Brian Rini, Vanderbilt) argued the benefit was too modest relative to the toxicity profile.

🧠 BPS Take: The split decision is less about two different drugs and more about two fundamentally different questions the FDA is wrestling with. The camizestrant vote was about whether the strategy of acting on a molecular signal before imaging shows progression is ready for primetime. The FDA essentially said: “you’ve shown that switching early extends PFS, but you haven’t shown it’s better than switching at progression, because you didn’t let the control arm access the drug”. That’s a very fair criticism, and I would be curious to see the communications between the FDA and AZN leading up to the launch of the study to better understand how far AZN strayed from the FDA’s guidance. Nonetheless, it is a novel effort by AZN to test switching upon ctDNA progression of a high frequency mutation. Pushing forth novel treatment paradigms is tough business and there are higher risks of their being bumps in the road. AZN may need to re-run this with a crossover-permitted design or wait for OS maturation, both of which cost lots of years and dollars.

What’s interesting is the contrast in how ODAC evaluated “meaningful benefit” across the two votes. In breast cancer, a 6.8-month PFS gain with a novel biomarker-guided paradigm wasn’t enough without OS. In prostate cancer, a 7.5-month PFS gain with an acknowledged toxicity burden passed 7-1. This feels like a broader commentary on where these two diseases are. Breast cancer has a deep bench of endocrine options and ODAC is fatigued by PFS-only approvals in that space, while PTEN-deficient mHSPC is a genomically defined population with genuinely limited options.

AZN will likely get the TRUQAP approval. For camizestrant, it wouldn’t be unprecedented for it to be approved in some fashion, however the negative ODAC vote, higher bar in breast cancer, and study design deficiencies pointed out in the meeting would make me think otherwise.

FDA Approves Arvinas’ Veppanu — First-Ever PROTAC Reaches Market, But Nobody Wants to Sell It

📅 May 1 | 🏢 Arvinas ( ), Pfizer ( ) | 💊 Veppanu (vepdegestrant) | 🏷️ Approval

The FDA approved Veppanu (vepdegestrant), a first-in-class PROTAC (proteolysis-targeting chimera), for second-line treatment of ER-positive, HER2-negative, ESR1-mutated metastatic breast cancer. PROTACs work by hijacking the cell’s natural waste disposal system to degrade disease-driving proteins — a fundamentally different mechanism than traditional drugs that block or activate targets.

But the approval comes with an unusual asterisk. Neither Arvinas nor its partner Pfizer plan to commercialize it themselves. The two companies originally had a 50-50 development and commercialization deal signed in 2021, envisioning a broad ER+ breast cancer franchise. When VERITAC-2 data narrowed the addressable market to just ESR1-mutated patients in the second-line setting, the economics of the partnership collapsed. Pfizer, for whom a niche monotherapy doesn’t move the needle, effectively walked away from commercialization. Arvinas, which has laid off nearly half its workforce across two rounds of cuts in 2025 and has no commercial infrastructure, can’t launch it alone. In September 2025, both companies agreed to out-license commercialization to a third party. They submitted the NDA to FDA anyway. As of the approval date, no commercialization partner has been announced — CEO Teel says one is expected “in the coming weeks.”

🧠 BPS Take: This is a genuinely strange moment. The first PROTAC ever approved by the FDA has no one lined up to sell it. This should be a much bigger moment, but the commercial story is a cautionary tale about what happens when your data narrows your label to a sliver of your original thesis. Arvinas stock popped ~7%, but the company is clearly pivoting its identity toward its earlier-stage PROTAC pipeline in Parkinson’s (ARV-102), NHL (ARV-393), and KRAS-driven solid tumors (ARV-806). I’m curious to see who picks this asset up and for how much. There are not many de-risked assets in oncology up for sale, albeit this one being in a much smaller market than originally anticipated. For whoever picks up the commercialization rights, the question is whether a first-in-class PROTAC in a narrow ESR1-mutant niche can separate from existing oral SERDs and build a meaningful commercial business.

Intellia Posts First Positive Phase 3 for In Vivo Gene Editing — Stock Down ~7% Since

📅 April 27 | 🏢 Intellia Therapeutics ( ) | 💊 Lonvo-z (lonvoguran ziclumeran) | 🏷️ Data Readout

Intellia reported positive Phase 3 HAELO results for lonvo-z in hereditary angioedema (HAE), marking the first successful Phase 3 trial for any in vivo CRISPR gene editing therapy globally. A single dose of lonvo-z reduced HAE attacks by 87% vs. placebo (p<0.0001) over a six-month evaluation period. 62% of lonvo-z patients were completely attack-free and therapy-free vs. 11% on placebo. Safety was clean — all adverse events mild or moderate, no serious AEs in the treatment arm. Intellia has initiated a rolling BLA submission and is targeting a U.S. launch in H1 2027.

🧠 BPS Take: This is a historic milestone, no doubt. An in vivo gene editing therapy registered a positive Phase 3 study. But the market’s reaction (stock down 7% as of this writing) tells a more nuanced story. Specifically, I think it reflects the “cell and gene therapy tax”. Lonvo-z’s efficacy is essentially identical to Takeda’s Takhzyro (lanadelumab), which also delivers 87% attack rate reduction with a nearly identical mean monthly attack rate (0.26 for lonvo-z vs. 0.3 for Takhzyro). The difference is that lonvo-z is a single IV infusion (a one time potential cure) and Takhzyro requires injections every 2–4 weeks for life. How will the rest of the stakeholders in the market view this? If you’re Intellia, you want them to see this as a curative therapy for a very serious illness, something no other competitor can claim. But perhaps if you are a payer or a competitor, you can look at lonvo-z and say it’s mostly an expensive convenience advantage. The aforementioned “tax” shows up on the efficacy line of a cell or gene therapy’s therapeutic product profile. While the lifetime expense of getting this drug vs. taking several injections very two to four weeks, favors the one-time treatment, the near-term financing of a likely $400K+ gene-editing drug is a massive pill for any payer to swallow. Especially if the efficacy is not numerically all that different from cheaper (albeit lifetime) therapies.

For cell and gene therapies to justify the pricing and payer negotiation headaches that come with one-time treatments, the market increasingly expects a big shift in outcomes. For other gene editing companies, the lesson here is indication selection and product strategy planning early on, before you go down the road of committing to a lead clinical asset or pivotal program, is paramount.

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Intellia also announced a $180M equity raise at $10.75/share simultaneously with the data, diluting shareholders right at the moment of maximum attention. The science delivered exactly what it needed to. The question is whether the commercial math works in a world where matching existing efficacy with better convenience may not be enough to command gene therapy economics.

Summit’s Harmoni-3 Interim Miss Sends Stock Down 25% — Ivonescimab’s Global Story Gets Murkier

📅 April 30 | 🏢 Summit Therapeutics ( ) | 💊 Ivonescimab | 🏷️ Data Readout

The squamous cohort of Summit’s Harmoni-3 trial — evaluating ivonescimab (PD-1/VEGF bispecific) plus chemo vs. Keytruda plus chemo in first-line metastatic NSCLC — missed statistical significance on PFS at a recently added interim analysis. The independent data monitoring committee recommended the study continue as planned. Summit noted the interim had a “meaningfully higher bar” than the final PFS analysis due to minimal alpha spent. Final PFS and interim OS readouts are still expected H2 2026.

🧠 BPS Take: Summit tried to add an interim analysis to accelerate a potential FDA conversation, and the bet didn’t pay off. I generally think it is a red flag when companies start rejiggering their statistical analysis plan mid study. The high statistical bar (likely ~0.001 alpha) means this miss doesn’t necessarily predict failure of the final readout, but it does mean the PFS effect size in the global trial may be weaker than what Akeso showed in the China-only studies. This was a big fear behind the entire thesis of Summit as a company. They are playing the China clinical data arbitrage game, but will China data look as good in a global (more western) population? Folks like Kailera, who recently IPO’d, pushing this same strategy with a portfolio of Chinese GLP-1s should take note.

The stakes for the Harmoni-6 (China) OS update at ASCO’s plenary session just got significantly higher. If OS is strong, it buffers some of the negative sentiment from this latest PFS slip. However if the OS disappoints, the PFS slip starts to feel like the canary in the coal mine. Merck, BMS, Pfizer and others who have flocked to PD-1xVEGF are all watching closely.

🌐 CONNECTING THE DOTS

When the outside world meets biopharma

FDA Commissioner Makary Launches Real-Time Trial Monitoring Pilot

📅 Date: 2026-04-28 | 🏢 Company: POLICY/MACRO | 💊 Drug/Asset: N/A | 🏷 Event Type: FDA Policy / Regulatory Reform

The FDA announced two proof-of-concept real-time clinical trials (RTCTs) that are already running, plus a Request for Information (RFI) for a broader pilot program launching this summer.

AstraZeneca is conducting the Phase 2 TRAVERSE trial testing Calquence (BTK inhibitor) + AbbVie’s Venclexta + rituximab in treatment-naïve mantle cell lymphoma. The FDA confirmed it has already received and validated real-time safety signals from this trial through software company Paradigm Health. Amgen is running a Phase 1b trial of Imdelltra (tarlatamab), its DLL3 T-cell engager already approved for extensive-stage SCLC, in limited-stage small cell lung carcinoma (STREAM-SCLC).

The FDA receives aggregated signals only, including adverse event rates, tumor response percentages, and pre-agreed efficacy endpoints. No raw patient-level data. Individual records stay with the sponsor. FDA Chief AI Officer Jeremy Walsh: “We’re not interested in seeing that patient-level data. What we’re interested in is, can the FDA make a regulatory decision on signals?”

Commissioner Makary said 45% of the time between Phase 1 start and approval submission is “dead time” (i.e. paperwork, analysis, formatting, and the gaps between discrete phase). He framed this explicitly as a competitiveness issue: China surpassed the U.S. in Phase 1 trial volume around 2021, and the growth since has been “exponential.” The stated ambition goes beyond speed — it’s about collapsing the traditional Phase 1 → 2 → 3 sequence into “continuous trials” by eliminating inter-phase hiatuses.

🧠 BPS Take: This is the most concrete output of the Makary FDA push to modernize the agency and use technology to speed up drug reviews. Name-dropping AstraZeneca and Amgen signals credibility and that Big Pharma sees value in the transparency-for-speed trade. But the real test is whether this scales beyond these two oncology indications, how these scale up to larger studies, and later on into other therapeutic areas.

The China point Makary makes is an important one too. Seeing how quickly China has outpaced the US in clinical trials, as well as the plethora of deals by US based entities to bring-in Chinese drugs, is serving as a helpful counterpoint to show how our systems can be improved. It’s rare in our political culture to look at other countries and think, “hey they seem to know what they’re doing over there, let’s try that at home” from a place of abundance. Instead we respond best to competition. The fear that we are falling behind in drug development, AI, and energy comes from a place of scarcity, but perhaps America’s love language is competition, and China knows just how to pull on our heart strings.

The Lp(a) Drug Race: Novartis’ Pelacarsen (Lp(a)HORIZON, 8,323 pts), Amgen’s Olpasiran, Eli Lilly’s Muvalaplin — H1 2026 Outcomes Data Imminent

📅 Date: April 27, 2026 (feature week) | 🏢 Company: Novartis ( ) / Ionis ( ) / Amgen ( ) / Eli Lilly ( ) | 💊 Drug/Asset: Pelacarsen (ASO, Lp(a)HORIZON Phase 3); Olpasiran/AMG-890 (siRNA, OCEAN Phase 3); Muvalaplin (oral small molecule, Phase 3) | 🏷 Event Type: Industry Feature — Late-Stage CV Outcomes Race

CNBC highlighted three major pharmaceutical companies racing to prove that lowering lipoprotein(a) (Lp(a)) reduces cardiovascular events, with pivotal outcomes data expected in the first half of 2026. Novartis and Ionis are leading with pelacarsen, an antisense oligonucleotide (ASO), in the Lp(a)HORIZON trial enrolling 8,323 patients. Topline results are expected in H1 2026. Amgen is running the OCEAN(a)-OUTCOME Phase 3 trial with olpasiran, an siRNA. Eli Lilly is developing muvalaplin, an oral small molecule that inhibits Lp(a) formation, currently in Phase 3.

Approximately 64 million Americans have elevated Lp(a), and there is currently no approved therapy specifically targeting this risk factor. Elevated Lp(a) is an independent cardiovascular risk factor associated with increased rates of heart attack and stroke, even in patients with well-controlled LDL cholesterol.

🧠 BPS Take: The H1 2026 outcomes data from Lp(a)HORIZON is the pivotal proof-of-concept for the entire Lp(a) field. Lowering Lp(a) does not automatically equal reducing cardiovascular events, but most KOLs will tell you they feel pretty good that doing so will reduce cardiac events. Still, this needs to be be proven in a large, adequately powered outcomes trial. Lp(a)HORIZON with 8,323 patients is the first trial designed to answer that question. If pelacarsen hits, it serves as a sigh of rlief to the whole field, validating this target as a key lever for cholesterol control and opening the competitive gates for the rest of the Lp(a) programs to follow suit. If it misses, the conversation shifts to whether Lp(a) needs to be pushed down even further in order to see hard outcomes benefits. Right now pelacarsen has demonstrated 80% reduction in P2 studies. Olpasiran (Amgen) and Lepodisiran (Lilly) have shown 95% and 94% respectively.

Lilly again has a sharp strategy in this arena. They aren’t sticking to just siRNA based treatment, as they have an oral Lp(a) inhibitor, muvalaplin, now enrolling a P3 outcomes study. As we’ve seen with the PCSK9 market, it has taken a long time for injectables (whether they be antibodies or siRNA) to gain market traction. For cholesterol control, it’s possible oral convenience may hold the advantage for commercial uptake.

As an aside, I was pleased to see Lp(a) get attention on a more generalist site like CNBC. I feel pretty confident Lp(a) reduction is clinically meaningful. Just hearing so many stories from cardiologist friends of mine of very young people dying of heart attacks, not knowing why, only to later find out that they were genetically predisposed to having very high Lp(a). The annoying part about this is that even if these trials read out positively, it is going to take some time for guidelines to change and for clinical practice to change to regularly test for it. Right now, even for LDL, we just get our LDL-c measured in our annual checkups, when it is pretty clear that ApoB100 is a much better measure of your bad cholesterol related risk.

In any case, if you are curious about your genetic predisposition to high Lp(a), you can go pay for a test yourself (as I did) at the behest of one my cardiologist friends. South Asians and African Americans tend to be the most at risk, thus why I felt the need to get mine checked out. Thankfully I am A-OK, but even if I wasn’t, I am excited that there will be new drugs soon that help to prevent Lp(a) related cardiac events.

Semaglutide Cuts Heavy Drinking by 41% in Lancet RCT — GLP-1s Open Another Therapeutic Front

📅 May 1 | 🏢 Novo Nordisk ( ) | 💊 Semaglutide (Wegovy) | 🏷️ Data Readout

A randomized, double-blind, placebo-controlled trial published in The Lancet showed once-weekly semaglutide 2.4 mg reduced heavy drinking days by 13.7 percentage points more than placebo over 26 weeks in 108 adults with obesity and alcohol use disorder. Semaglutide also reduced total alcohol consumption (467.5 g/30 days difference), drinks per drinking day, self-reported cravings, and multiple alcohol biomarkers including phosphatidylethanol (p<0.0001). Safety was consistent with known GI side effects. The trial was conducted at Mental Health Center Copenhagen and funded in part by Novo Nordisk.

🧠 BPS Take: The anecdotal evidence has been accumulating for years. Now there’s a properly controlled Lancet RCT confirming it. GLP-1s reduce alcohol consumption. Importantly, this was a small trial (n=108), in patients with both obesity and alcohol use disorder, at a single site in Denmark. Less than 2% of people with alcohol use disorder in the U.S. use pharmacotherapy. If larger trials replicate this, Novo and Lilly have a potential indication that could expand GLP-1 addressable market well beyond obesity and diabetes into behavioral health. That’s exactly what Lilly is betting on with brenipatide, its once-monthly GLP-1/GIP agonist. The key question that remains for me is that will this still work in patients who are not obese? What does this say about breaking addiction to other vices that are not calorie-driven or food-like (e.g. smoking, opioids, etc.)?

💰 FOLLOW THE MONEY

Deals, dollars, and what they signal

M&A Bundle: Sun/Organon $11.75B (India’s Largest US Pharma Acquisition) + Lilly/Ajax $2.3B (Type II JAK2) + Ligand/XOMA $739M (Royalty Aggregation)

📅 Date: April 26-27, 2026 | 🏢 Company: Sun Pharmaceutical Industries / Organon ( ); Eli Lilly ( ) / Ajax Therapeutics; Ligand Pharmaceuticals ( ) / XOMA Royalty ( ) | 💊 Drug/Asset: Organon portfolio (Nexplanon, biosimilars, legacy brands); AJX-101 (Type II JAK2 inhibitor, Phase 1); XOMA royalty portfolio (200+ assets, 7 commercial) | 🏷 Event Type: Acquisition (All-Cash x2; Milestone-Based x1)

Sun Pharmaceutical Industries announced a definitive agreement to acquire Organon for $14.00 per share in cash, representing a 24% premium and an enterprise value of $11.75B. The deal, announced Saturday evening April 26, is India’s largest-ever acquisition of a U.S. pharmaceutical company. Organon’s portfolio includes Nexplanon (the #1 contraceptive implant in the U.S.), a biosimilars business, and legacy women’s health brands. The transaction is expected to close in early 2027, making Sun Pharma the third-largest global women’s health company.

Eli Lilly announced on April 27 that it will acquire Ajax Therapeutics for up to $2.3B in milestone payments. Ajax is developing AJX-101, a Type II JAK2 inhibitor in Phase 1 for myelofibrosis and polycythemia vera. Type II JAK2 inhibitors represent a mechanistic differentiation from all currently approved JAK inhibitors (ruxolitinib, fedratinib, pacritinib, momelotinib), which are Type I. This is Lilly’s sixth acquisition of 2026.

Ligand Pharmaceuticals announced on April 27 that it will acquire XOMA Royalty for $39.00 per share in cash, representing approximately a 3% premium and an equity value of $739M. The combined entity will hold royalty interests in over 200 partnered programs, including seven commercial products. The transaction is expected to close in Q3 2026.

🧠 BPS Take: Three completely different M&A logics playing out in the same 48-hour window.

Sun Pharma is making a bold move, signaling that they are not satisfied staying in India, and want to have a foothold in the US market and expanding its business into speciality areas, like women’s health. Raising $7.75B in debt to take out Organon could either be really smart or look really dumb in retrospect. Still, this is a major sign that one of India’s largest drug makers is ready to make waves in the US specialty market. Organon gives them a top-3 global women’s health franchise, a U.S. commercial infrastructure, and a biosimilars platform.

Lilly is buying yet another early clinical phase asset, this time a Type II JAK2 inhibitor for myelofibrosis. The idea here is that this strategy may overcome resistance mechanisms seen with Type I inhibitors (ruxolitinib, etc.). It still baffles me that for all the innovation we have had in oncology, myelfoibrosis is still treated largely with a series of slightly different flavors of JAK inhibitors. Nonetheless, here is Lilly continuing its trend of taking multiple shots on goal on early science well-before any of their GLP-1 patent cliffs hit. If AJX-101 shows activity in post-ruxolitinib myelofibrosis patients, this could quickly climb the JAK inhibitor hierarchy. If it doesn’t, Lilly writes off the milestones and moves on. A billion or two here and there as a write-off is just chump change for them.

Ligand/XOMA is pure financial engineering, aggregating royalty streams as an asset class. Post-deal, Ligand will have 200+ royalty assets generating predictable cash flows with minimal operational risk. These royalty businesses have done incredibly well and might be a win-win for later-stage biotechs, giving them a lifeline to large amounts of upfront non-dilutive capital. Notably Revolution Medicines did a royalty financing deal back in June 2025 with Royalty Pharma, netting them $2B upfront in exchange for tiered declining royalties on daraxonrasib for 15 years. The royalties drop to zero once annual sales exceed $8B. All signs point to them meeting or exceeding that mark. Owl Posting had a nice deep dive on these sorts of synthetic royalty deals and other methods of financial engineering in Biotech that I highly recommend reading if you want to learn more about this topic and how it fits into the broader architecture of innovation.

Triple Biotech IPO Surge: Seaport $255M (SPTX), Hemab $302M (COAG), Avalyn $300M (AVLN, +44% debut) — $850M+ Raised, Strongest Market Since 2021

📅 Date: April 27-30, 2026 (week) | 🏢 Company: Seaport Therapeutics ( ) / Hemab Therapeutics Holdings ( ) / Avalyn Pharma ( ) | 💊 Drug/Asset: Seaport neuropsychiatry pipeline (PureTech spinout); Hemab coagulation portfolio (Glanzmann thrombasthenia, Von Willebrand Disease); Avalyn inhaled IPF treatments | 🏷 Event Type: Triple Biotech IPO Pricing — All Three Upsized

Three biotech companies priced upsized IPOs during the week of April 27, collectively raising over $850M and signaling the strongest biotech IPO market since 2021. Seaport Therapeutics raised $255M by pricing 14.16 million shares at $18, upsized from an initial target of $212.4M. The company, a PureTech spinout, is developing a neuropsychiatry pipeline. Hemab Therapeutics Holdings raised $301.5M by pricing 16.75 million shares at $18, upsized from an initial target of $200M. The company, backed by Novo Holdings, is developing treatments for rare coagulation disorders including Glanzmann thrombasthenia and Von Willebrand Disease.

Avalyn Pharma raised $300M at $18 per share and surged 44% on its debut to close at $26, giving the company a market capitalization of approximately $1.1B. Avalyn, also backed by Novo Holdings, is developing reformulated inhaled treatments for idiopathic pulmonary fibrosis (IPF). The three IPOs bring Q1 2026 total biotech IPO proceeds to approximately $2.2B, according to industry trackers.

🧠 BPS Take: These three IPOs are a strong sign that the IPO window is open and public market investors have an appetite for mid to late stage drug companies again. A psych company, a pulmonary disease company, and a rare disease company, quite a diverse grouping, all doing well on their first days of trading is a signal that investors are willing to take risk across many therapeutic areas, and not just the hot areas like GLP-1s. Watch for more IPOs in Q2 2026 if this momentum holds.

Back next week with more BioPharma strategy takes! Share this with a friend of colleague if you found it helpful.

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Earlier this month a new prediction market got a lot of attention on X. It’s called Endpoint Arena. Similar to other prediction markets, like Kalshi and Polymarket, it allows users to place ‘Yes’ or ‘No’ wagers on particular outcomes, only for Endpoint Arena, their menu of markets strictly focuses on clinical trial results. Endpoint Arena specifically appears to be interested in testing whether the frontier AI models can predict clinical trial outcomes, how these models’ prediction abilities compare to one another, and conceivably (from the image below) provide humans an opportunity to make Yes/No bets on the outcomes of specific trials.

The unveiling of this new offering was expectedly divisive, but I think it emerged at the right place and right time for that lightning rod reaction. In fact, the major predictions markets have had similar offerings for a while now. Real-money wagering on drug-related regulatory events is already happening. With Substack’s Polymarket integration, I’ve pulled in a few examples below:

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I held my tongue on this topic because I was still trying to figure out how I feel about all this, as it sort of sits at the intersection of two different passions of mine: drug development and sports betting.

I think I have broad definition of what “gambling” or “betting” is. Sports betting, prediction markets, buying/selling stocks, buying/selling options, etc. all fit under gambling to me. You can lose a lot of money doing all of the above, but if you educate yourself on the right strategies to implement, are incredibly data-driven, and know the right healthy risk-threshold for you, you can do quite well. Every decision we make on a daily basis is either an implicit or explicit calculation of risk and probability. I don’t think any of the above forms of betting are that different.

So look, I am not anti-gambling. It is a vice and should be approached with extreme caution and moderation. Some people shouldn’t be sports betting, just like some people shouldn’t be drinking, just like some people shouldn’t be trading stocks, and just like some people shouldn’t be smoking weed. But if you are able to maintain a healthy relationship with these vices, and not letting them imbalance you in deleterious ways - it’s a free country, you do you.

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Nor am I anti-markets. When markets function healthily, with transparency, right-sized regulation, competition, and proper enforcement against corruption, they can accelerate innovation and create tremendous value for both business and consumers.

To help me get to the bottom of how I feel about prediction markets for clinical trials, I structured my thinking around a few questions:

• What can we learn from how sports betting markets work?

  • Note: 90%+ of the trading volume on prediction markets is actually from sports. Kalshi and Polymarket are in large part sports betting exchanges. Sports books and sports betting exchanges, have been around a long time and are the best analog we can glean insights from.

• How is Material Non-Public Information (MNPI) different in clinical trial markets?

• What is the reality of enforcement in these sorts of prediction markets?

• Do these markets align with the overall goal of making successively more types and better kinds of drugs that help people who are sick?

Let me explore each one with you.

The Sports Betting Analogy

Prediction markets and sports betting share some structural DNA. Typically with sports betting you are wagering against “The House”. These are betting platforms like FanDuel, DraftKings, Caesars, PrizePicks - pretty much any second or third advertisement you would see when watching a sporting event. Generally these sorts of companies make money by charging a “vig”, also known as a “spread”.

In the above example, you can either bet the Cardinals to win by 7 or more points (e.g. -6.5) or the Saints to win OR lose by less than 7 points (e.g. +6.5). Both wagers have a price of -110. This is just a funky way that sports books display probabilities. It essential means if you bet $110 you profit $100. If you convert this to percentages, the sports book is saying they think there is a 52.4% chance that Cardinals -6.5 line hits and a 52.4% chance the Saints +6.5 line hits. If you’re following along, that adds up to 105%, which doesn’t make any sense. But that right there is the “vig”. The sports book is trying to solicit equal action on both sides of the bet. If they get $110 on the Cardinals and $110 on the Saints, they’ve collected $220. If the Saints side hits, they need to pay out $210 ($110 wager plus a $100 profit) to the people who bet the Saints. That leaves the sports book with a profit of $10 (a vig of ~5%), paid for by the people who took the Cardinals and lost the bet. Make sense? Sports books are constantly adjusting vigs and odds on each market they create to optimize their potential ROI, by balancing the amount of money on both sides of a bet such that no matter what the outcome is, they make a small profit.

Prediction markets function a bit differently than sports books. Instead of betting against Kalshi or Polymarket, you are betting against other people on those apps. Individuals more or less get to set their own lines and the app basically pairs you up with someone (or many someones) on the other side of the transaction. It similar to when you buy or sell a stock on E*TRADE. If I buy 100 shares of Eli Lilly stock, I am buying that from one or more people or entities out there on the internet who I’ll never meet. If you are betting $100 on Cardinals, Kalshi and Polymarket software finds people who collectively have $100 on the Saints. In exchange they charge you a small fee (1-3%). The value of your position can then go up or down based as it gets closer to the final outcome. Because you’ve essentially turned your prediction into a stock, you can trade in/out of that position up until the final outcome of the game is known. So for instance if the Cardinals are blowing out the Saints in the third quarter, my position may be worth more than what it was at the start of the game. I might decide to sell my position before the end of the game just to look in a profit and avoid losing my money to an albeit unlikely late-game comeback by the Saints.

These sorts of exchanges are far more fair on the surface, but much harder to make money on, because you are competing against a lot of smart people who are way better at this than the average person. We call these people “sharps”. They’re typically hedge funds, trading firms, and professional bettors. Just sticking to sports, the typical professional sports bettor hits roughly 53–55% of their bets. That’s a slight edge that they compound over time with volume. Most of the time, they have proprietary algorithms and models. Their formulas look at very obscure parts of the game or track very specific sets of data that may give them an edge and may not be underweighted in the public market.

For example, in basketball there were some famous sports bettors who tracked NBA referees’ foul patterns with regard to specific players. This gave them an edge that wasn’t necessarily priced into sports betting lines. Eventually, the sports book gets smart and incorporates these components into their market-making strategies, and the professional sports bettor needs to find a new edge. In certain cases they may have advanced notice on player injuries, lineup news, or any other material information that hasn’t made its way to the public yet (more on this later).

Too soon? Tip me.

In the sports world, these markets tend to be more accurate, but it requires one main thing: liquidity. The more money that is trading hands within a particular market, the higher confidence you have in the probabilities that that market displays. Thin markets (total value in the hundreds of dollars) are typically noisy and often incorrect. It’s not just the sheer volume of money exchanging hands that makes a market better at predicting the future. It’s really these expert bettors who are driving the probabilities. If the entire market was a bunch of people only betting 25 bucks a bet on a sport they’d never heard of, over time the market would probably not be all that predictive. Sharps are the ones betting the largest sums of money, but also have the strongest predictive value. But like I said before, even the best predictors of the future (in sports) are right at best 55% of the time.

This liquidity piece, as well as the expertise/sharpness piece, is really important when we think about clinical trial markets. In order for these markets to be really good at predicting clinical trial outcomes, they would need to attract large volumes of money, but also a sufficient volume of sophisticated participants, to produce a meaningful outcome. The Science Policy Forum paper (Packin & Rabinovitz, April 2026) makes this exact point: thin liquidity means even small trades can manufacture the appearance of consensus, turning “forecasts” into instruments of influence.

To give you an example of how thin markets can be easily manipulated, let’s take the example I shared earlier about the market for the FDA approving retatrutide this year. If you go to that page on Polymarket, there’s an 18-cent price (aka 18% chance) that the approval happens this year. However, if you bet a relatively small sum of $1,000, the average probability of that event occurring would swing all the way to ~59% (this is where it says “Avg. Price 59-cents”). So just with a $1,000 bet I could move the market here by over 40 points. This tells you that this is a very thin market.

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We’re back for another edition of Last Week Tonight in BioPharma (LWTB)!

In case you’re new, here is what I am trying to do with this series:

1. A short recap of the most interesting stories from the past week with strategic insights to get you ready for your Monday meetings.

2. Up to 3 key events per category:

   • Press Release Decoder: going beyond the company speak, reading between the lines, thinking about what isn’t being said, to illustrate the strategic implications of a company’s moves that don’t make it into the press release

   • Connecting the Dots: looking at stories that are either about the macro or from the mainstream news and how they may impact BioPharma

   • Follow the Money: quick takes on some key deals that were struck and what they mean for those companies, their competitors, or the sector at-large

3. Free to all subscriber levels! Although if you like my free content and have $8/month to spare (or expense to your company), I think you’ll love the deeper analyses my paid subscribers get. You can upgrade at any time by entering your email in the box below.

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📡 PRESS RELEASE DECODER

What the press releases actually mean

FDA Approves Regeneron’s Otarmeni for Genetic Hearing Loss — The First Gene Therapy to Restore Neurosensory Function to Normal Levels, Offered at No Cost

📅 Date: 2026-04-23 | 🏢 Company: Regeneron Pharmaceuticals (REGN) | 💊 Drug/Asset: Otarmeni (lunsotogene parvec-cwha); AAV-based gene therapy; OTOF gene replacement; severe-to-profound sensorineural hearing loss | 🏷 Event Type: FDA Accelerated Approval (CNPV Program)

The FDA granted accelerated approval on April 23 for OTARMENI (lunsotogene parvec-cwha), making it the first gene therapy approved for OTOF-related hearing loss and the second new molecular entity approved under the FDA’s Commissioner’s National Priority Voucher (CNPV) program. The therapy is indicated for pediatric and adult patients with severe-to-profound sensorineural hearing loss caused by biallelic variants in the OTOF gene, preserved outer hair cell function, and no prior cochlear implant. Regeneron announced it will provide OTARMENI at no cost to clinically eligible U.S. patients.

Approval was based on the pivotal CHORD trial, which enrolled 20 participants aged 10 months to 16 years who received a single intracochlear infusion — a procedure similar to cochlear implantation. The trial’s primary endpoint was met: 80% of participants (16 of 20) achieved hearing improvement at or better than ≤70 dB HL pure tone audiometry at 24 weeks. Seventy percent (14/20) achieved auditory brainstem response ≤90 dB at 24 weeks, meeting the key secondary endpoint. Among the 12 participants followed to 48 weeks, 42% (5/12) achieved normal hearing including whispers (≤25 dB HL) — a remarkable threshold for a disease that was previously managed only with assistive devices.

OTOF-related hearing loss affects approximately 50 newborns per year in the United States, making it ultra-rare even by orphan disease standards. The condition involves a non-functioning otoferlin protein critical for communication between inner ear sensory cells and the auditory nerve. OTARMENI uses a modified, non-pathogenic AAV vector to deliver a working copy of the OTOF gene into cochlear hair cells, with expression restricted via a proprietary Myo15 promoter. Continued accelerated approval is contingent on results from the ongoing confirmatory portion of the CHORD trial. Common adverse reactions (≥5%) included otitis media, vomiting, nausea, dizziness, and procedural pain. The approval coincided with Regeneron’s announcement of a Most-Favored-Nation (MFN) drug pricing deal with the Trump administration.

BPS’ Take: Let me separate the science from the politics here, because both are actually significant in their own right. On the science: this is a genuinely impressive efficacy for a gene therapy in a neurosensory indication — 42% of patients achieving normal hearing including whispers at 48 weeks is the kind of outcome that justifies the “transformative” language usually deployed too liberally in biopharma press releases. The CHORD trial is small (n=20), it’s accelerated approval with confirmatory data pending, and the 12-month durability data is still immature. But the results are real.

On the politics side of the equation, this clearly feels like a carefully choreographed quid pro quo with the Trump administration. Trump is focused heavily on the optics (not the substance) of lowering drug prices. By providing OTAREMNI for free and agreeing to cut prices of its PCSK9 inhibitor (PRALUENT), Regeneron get’s to avoid the 100% tariff that was looming over its head for three years. It’s likely a small concession for REGN to make. OTARMENI affects roughly 50 infants per year (small market). The price cut via MFN is likely discounting PCSK9 down to what they were already offering behind the scenes to payers. So again - it’s a win on the optics for Trump and not that big a concession for Regeneron.

For such a small indication, Regeneron may feel they have more to gain with the positive PR and “being a force for good” than trying to do the work of selling this drug (negotiating with payers, building a sales team, marketing, etc. etc.). Perhaps this engenders good faith with regulators down the road for future gene therapies. Using a loss-leader to boost your reputation with key customers/stakeholders is uncommon in major markets, but it is a strategy used by consumer tech companies all the time. Amazon has done this to the nth degree, selling other product lines to consumers at cost or at a loss, simply to drive up Prime membership growth.

Importantly, while the drug cost itself will be free, the cost of administration, surgical delivery, follow-ups, and other expenses aren’t being covered by Regeneron. I am not saying they should be either, just that for the 50 people a year with this horrible disease, there is still going to be significant costs associated with getting this treatment. It’s not exactly “free”.

The less salient impact of Regeneron’s decision falls on their small biotech competitors. Regeneron has placed a significant barrier for smaller biotechs that could be competitors (i.e. Sensorion, Akouos, and Sound Biologics, to name a few). Giving something away for free is a luxury only mega companies can afford. You see this in a more altruistic sense for global health. For instance, Gilead selling its long-acting HIV prevention drug, lencapavir, at-cost in low-and-middle-income countries. Smaller players trying to develop a drug in OTOF-related hearing loss now need to rethink their corporate strategy. If the benchmark is “free 99”, it makes developing a new treatment in this space less palatable, thus hindering innovation.

Buy Me a Drank 🎵 (T-Pain voice)

Revolution Medicines’ Daraxonrasib Shows 58% ORR in First-Line Pancreatic Cancer at AACR — Phase 3 RASolute 302 Results Headed to ASCO Plenary

📅 Date: 2026-04-21 | 🏢 Company: Revolution Medicines (RVMD) | 💊 Drug/Asset: Daraxonrasib (RMC-6236); oral RAS(ON) multi-selective inhibitor; Phase 1/2 first-line metastatic PDAC; Phase 3 RASolute 302 (met primary + key secondary endpoints) | 🏷 Event Type: Phase 1/2 Clinical Data Readout (AACR Late-Breaking Mini-Symposium) + Phase 3 ASCO Plenary Announcement

Revolution Medicines presented updated Phase 1/2 data from two trials of daraxonrasib at the AACR Annual Meeting in San Diego on April 21, 2026. In the RMC-GI-102 combination cohort, 40 patients with previously untreated RAS-mutant metastatic pancreatic ductal adenocarcinoma (PDAC) received daraxonrasib 200 mg once daily plus gemcitabine and nab-paclitaxel (GnP) in a Day 1/Day 15 schedule. As of a December 1, 2025 data cutoff (≥18 weeks follow-up), the confirmed objective response rate (ORR) was 58% (95% CI: 41–73%), including one complete response. The 6-month Kaplan-Meier PFS estimate was 84% (95% CI: 68–93%); the 6-month OS estimate was 90% (95% CI: 76–96%). Grade ≥3 treatment-related AEs included anemia (33%), decreased neutrophil count (20%), and fatigue (18%), with no Grade 5 TRAEs.

In the monotherapy cohort (RMC-6236-001), patients with previously untreated RAS-mutant metastatic PDAC received daraxonrasib 300 mg daily, achieving a 47% ORR (95% CI: 31–64%) with a disease control rate of 92% (95% CI: 79–98%). Six-month PFS was 71% and 6-month OS was 83%. Separately, Revolution announced the pivotal Phase 3 RASolute 302 trial data — in previously treated metastatic PDAC — will be presented at the ASCO 2026 plenary session; the company had earlier confirmed this trial met all primary and key secondary endpoints, including both PFS and OS. Revolution raised $2.0 billion in concurrent stock and convertible note offerings in mid-April, with shares trading around $142, following the Phase 3 data announcement.

Pancreatic cancer is one of oncology’s hardest problems: approximately 60,000 new U.S. cases annually, ~80% diagnosed at advanced or metastatic stage, 5-year survival for metastatic disease approximately 3%. More than 90% of PDAC tumors harbor RAS mutations, making this cancer the most RAS-addicted of all major tumor types. Daraxonrasib is one of four global Phase 3 trials Revolution is running in PDAC and NSCLC, alongside zoldonrasib (KRAS G12D-selective), which also showed Phase 1 data in KRAS G12D NSCLC at AACR this week.

BPS’ Take: This is continued validity for Revolution Medicine’s platform, pipeline, and lead product. 58% ORR in 1L PDAC is remarkable, especially when you consider chemotherapy-alone typically nets a 25-35% ORR. These data provide important signal to what daraxonrasib’s clinical profile may look like in the P3 RASolute 303 study, which began recruiting earlier this year.

Everyone’s attention now draws to ASCO, where we are going to see the full results from the pivotal P3 RASolute 302 study (2L+ PDAC). Last week, we learned that the study hit on PFS and OS. I imagine when we see the KM curves, you’ll be able to fit an iceberg in between them. Both the AACR data and forthcoming ASCO data continue to justify RVMD asking for such a high price when they were shopping themselves in January, and perhaps portend an even greater rise in the company’s market cap upon launch. If the 2L+ PDAC data look as good as we think they will, that is having a halo effect on daraxonrasib’s 1L PDAC product profile as well.

Lilly Tumbles on Foundayo’s Shaky First Full Week — Oral GLP-1 Price War Gets Its First Scorecard

📅 Date: April 25, 2026 | 🏢 Company: Eli Lilly (LLY), Novo Nordisk (NVO) | 💊 Drug/Asset: Foundayo (orforglipron), oral small-molecule GLP-1 agonist; Oral Wegovy (semaglutide), oral peptide GLP-1 agonist | 🏷 Event Type: Commercial Launch Data / Stock Movement

Eli Lilly shares fell nearly 5% on Friday after IQVIA weekly prescription data showed Foundayo — the first oral small-molecule GLP-1 approved for obesity — generated 3,707 U.S. prescriptions for the week ending April 17, its first full week on the market. That figure jumped from 1,390 prescriptions recorded over the drug’s initial two days of availability following its April 6 launch, but fell short of the bullish trajectory investors had modeled. For comparison, Novo Nordisk’s rival oral Wegovy tablet hit 3,071 prescriptions in its first full week and then surged to 18,410 the following week, per IQVIA data shared by RBC Capital Markets analyst Trung Huynh.

The prescription shortfall prompted a meaningful recalibration of 2026 sales expectations. According to Huynh, some investors had initially projected as much as $5 billion in 2026 Foundayo sales; those estimates are now being pulled back to a $1.3-1.5 billion range — a number achievable if approximately 300,000 prescriptions are written by year-end. Lilly’s stock decline contrasted sharply with Novo Nordisk, which rose 7% on the same day as the market interpreted the data as a relative win for oral Wegovy’s early commercial trajectory. Foundayo is priced at $149/month through LillyDirect, compared to Novo’s oral Wegovy subscription at $249/month.

BPS’ Take: Let’s pump the brakes on both the panic and the celebration here. It’s way too early to write-off FOUNDAYO. One week of IQVIA data is a snapshot of how quickly the prescription fulfillment pipeline filled during the first seven days of a brand-new drug with a brand-new NDC code hitting pharmacy systems for the first time. Week 1 and Week 2 numbers are dominated by logistics, wholesaler stocking, pharmacy adjudication setup, prior authorization workflows, and LillyDirect fulfillment ramp. The real signal won’t emerge until we see Weeks 4-8, when the channel friction normalizes and we’re measuring actual patient starts.

That said, the comparison to oral Wegovy’s first-week trajectory is the number that matters to Wall Street, and Lilly lost that round. Novo hitting 3,071 in its first full week and then 18,410 the next week shows an acceleration curve that FOUNDAYO hasn’t demonstrated yet. It is still early innings in the oral GLP-1 battle. Much more cards left for both of these players to play.

🌐 CONNECTING THE DOTS

When the outside world meets biopharma

Trump’s MFN Drug Pricing Framework Is Now Complete — 17 Pharma Giants Have Signed, a 100% Tariff Looms July 31 for Holdouts, and Daiichi Sankyo Just Blinked

📅 Date: 2026-04-23 / 2026-04-24 | 🏢 Company: POLICY/MACRO + Regeneron (final signatory) + Daiichi Sankyo (tariff casualty) | 💊 Drug/Asset: All patented pharmaceuticals; MFN pricing; Daiichi Sankyo oncology portfolio (Enhertu, Datroway) | 🏷 Event Type: Thematic Bundle — Drug Pricing Policy + Pharma Tariff Shock

The Trump administration’s Most-Favored-Nation (MFN) drug pricing framework reached a symbolic milestone on April 23 when Regeneron signed as the seventeenth major pharmaceutical company to enter the deal. The MFN structure requires participating companies to offer Medicaid the same net prices as the lowest prices charged to other developed nations, in exchange for a three-year exemption from pharmaceutical tariff mandates. Among the terms in the Regeneron-specific deal: PRALUENT (alirocumab) will be offered at $225/month via TrumpRx.gov, and OTAREMNI will be provided free. The roster of signatories includes Pfizer, Johnson & Johnson, AstraZeneca, Novo Nordisk, Eli Lilly, Sanofi, and other major global manufacturers.

Companies that have not signed face a graduated 100% tariff on patented pharmaceutical products, with a July 31, 2026 effective date for large companies and September 29, 2026 for smaller companies. Generic pharmaceuticals, U.S.-origin products, and specialty categories are exempt. The United Kingdom negotiated a separate 0% tariff exemption in early April in exchange for agreeing to 25% higher net prices for new U.S. patented drugs sold in the UK — a structural template for other countries potentially under negotiation. Japanese pharmaceutical companies, including Daiichi Sankyo, are currently subject to a 15% tariff under the prevailing trade structure applicable to Japan/EU, with no MFN deal signed.

The tariff pressure crystallized dramatically on April 24 when Daiichi Sankyo — whose ADC portfolio includes ENHERTU (trastuzumab deruxtecan, co-developed with AstraZeneca) and Datroway — announced a two-week delay to its annual earnings report, pushing the disclosure from April 27 to May 11, 2026. The company cited the need to “review supply plans amid rapidly changing business conditions” and to deliberate on “loss provisions related to CDMO contracts.” Daiichi’s Tokyo-listed shares fell nearly 10% to a four-year low (weakest level since March 2022). The company has U.S. manufacturing operations in Ohio (fill-finish, packaging) and New York, but has not signed an MFN pricing deal, leaving its oncology franchise exposed to tariff uncertainty.

BPS’ Take: The MFN framework is simultaneously less and more than it appears. Less than it appears: most companies signing these deals are doing so on terms that affect a fraction of their revenue — Medicaid represents roughly 20–25% of U.S. drug revenue for most large pharma companies, and “most-favored-nation” pricing in practice often just mirrors deals already made with PBMs. The real financial exposure is narrow. More than it appears: the tariff mechanism is a structural forcing function that is visibly reshaping global pharma supply chain strategy. Daiichi Sankyo delaying earnings to model CDMO contract provisions suggests real revenue and cost uncertainty in their operational planning. The companies that hurt most here are mid-size ex-US BioPharmas without U.S. manufacturing and without the political leverage to negotiate MFN deals. The big players have largely adapted. The secondary effects on CDMO contracts and supply chain restructuring are where I’d be watching most carefully.

🚨 Trump Signs Weekend Executive Order on Psychedelics — FDA Issues Three CNPVs and Clears First U.S. Ibogaine Derivative Trial by Week’s End

📅 Date: 2026-04-18 (EO signed, 🚨 weekend break) / 2026-04-24 (FDA response) | 🏢 Company: POLICY + Multiple (Compass Pathways, atai Life Sciences, MindMed, DemeRx NB) | 💊 Drug/Asset: Psilocybin (treatment-resistant depression, MDD), methylone (PTSD), noribogaine (alcohol use disorder) | 🏷 Event Type: 🚨 Thematic Bundle — Executive Order (Weekend) + FDA Regulatory Action (Week)

President Trump signed an executive order on April 18, 2026 — a Saturday — directing the Department of Health and Human Services to accelerate access to psychedelic drug treatments for serious mental illness. The order instructed the FDA to issue Commissioner’s National Priority Vouchers (CNPVs) to psychedelic drugs with Breakthrough Therapy designation, with a focus on treatment-resistant depression, PTSD, and alcohol use disorder. Veterans’ access was specifically highlighted. By April 24, the FDA had responded with concrete regulatory action: CNPVs were issued to three programs (a company studying psilocybin for treatment-resistant depression, a company studying psilocybin for major depressive disorder, and a company studying methylone for PTSD). The FDA also cleared the first U.S. clinical study of noribogaine hydrochloride — an ibogaine derivative — for DemeRx NB in a Phase 1 trial for alcohol use disorder. Additionally, the FDA announced it will release final clinical trial design guidance for serotonin-2A agonists “imminently.”

Psychedelic biotech stocks including Compass Pathways , atai Life Sciences , and MindMed benefited from the sentiment lift following the EO. The Guardian published a piece on April 24 noting that “Trump psychedelics order largely symbolic, analysts say,” reflecting skepticism about whether regulatory velocity will actually accelerate meaningfully versus generating favorable optics. The CNPV program — originally designed for drugs in underserved indications — has now issued 18 vouchers and approved 4 products.

BPS’ Take: A weekend executive order generated a week of positive stock movement for psychedelic biotechs, followed by a set of FDA actions that are real but limited in their near-term impact. It’s hard not to look at this administration’s record and think that this EO isn’t a clear signal that psychedelics are a priority for the administration, which may make it easier for these drugs to get approved. It’s also troubling that famous people like Joe Rogan can just hit up the president and talk his ear off about psychedelics and all of a sudden improve the prospects of this entire class getting approved. If you’ve read BPS for some time now, you know that I’m quite bullish on the psychedelic space overall, especially with regards to novel next-gen psychedelics based off of traditional recreational compounds. However, I’m bullish on it because the data is so profound. Just because this administration seems more easily influenced and willing to curry favors, we can’t let that sacrifice data quality and rigorous testing of these compounds, as great data is still needed to drive necessary uptake in the market.

🚨 Pfizer’s Chief Strategy and Innovation Officer Andrew Baum Exits — The Analyst-Turned-Strategist Departs After Two Years Without a Clear Successor

📅 Date: 2026-04-20 | 🏢 Company: Pfizer (PFE) | 💊 Drug/Asset: N/A — executive departure | 🏷 Event Type: 🚨 Executive Departure

Pfizer announced that Andrew Baum, the company’s Chief Strategy and Innovation Officer (CSIO), will leave the company by the end of 2026 and is currently transitioning to a new, unspecified role. Baum, a former top-ranked sell-side pharmaceutical analyst at Citi, was hired by CEO Albert Bourla in 2024 to lead a strategic overhaul of Pfizer’s direction following the collapse of COVID-era vaccine and antiviral revenues. Baum spent approximately two years in the CSIO role before the departure announcement. No successor has been named. STAT News reported on the departure with coverage framing the exit as a loss of a high-profile external hire “brought on to revitalize Pfizer’s strategy.”

BPS’ Take: Two years is a short tenure for a C-suite role at a company of Pfizer’s scale, and the timing of this departure seems peculiar. Pfizer is STILL working through the post-COVID financial recalibration, integrating its Seagen acquisition, navigating the new MFN pricing environment, and building out a new pipeline. Baum was brought in as a signal of strategic transformation, but Pfizer’s prospects haven’t seemed to get much better from the outside looking in. This departure reminds me of when an NFL head coach fires his offensive coordinator to signal to the media that the direction of team is about to change. However, as I’ve written in the past, the problem might be at the top. Bourla has significantly underperformed relative to his peers.

In the current environment, Pfizer’s strategic challenges are less about having a brilliant Chief Strategy Officer and more about portfolio execution. It spent a lot of money on Seagen, but that $40B acquisition needs to start showing some major positive traction, otherwise it will look like it was all for naught. Ongoing Phase 3 studies with its PD-1xVEG-F program will also play huge role, as well as Pfizer making sure they can turn their GLP-1 assets from Metsera into a real threat to Novo and Lilly.

💰 FOLLOW THE MONEY

Deals, dollars, and what they signal

…A quiet week on the deals front. Hopefully more activity next week!

That’s a wrap on this week’s Last Week Tonight in BioPharma. If something here made you think, argue, or spit out your coffee — forward it to a colleague. See you next week!

We’re back for the fourth edition of Last Week Tonight in BioPharma (LWTB)!

In case you’re new, here is what I am trying to do with this series:

1. A short recap of the most interesting stories from the past week with strategic insights to get you ready for your Monday meetings.

2. Up to 3 key events per category:

   • Press Release Decoder: going beyond the company speak, reading between the lines, thinking about what isn’t being said, to illustrate the strategic implications of a company’s moves that don’t make it into the press release

   • Connecting the Dots: looking at stories that are either about the macro or from the mainstream news and how they may impact BioPharma

   • Follow the Money: quick takes on some key deals that were struck and what they mean for those companies, their competitors, or the sector at-large

3. Free to all subscriber levels! Although if you like my free content and have $8/month to spare (or expense to your company), I think you’ll love the deeper analyses my paid subscribers get. You can upgrade at any time by clicking the button below.

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And with that, let’s get into what happened this past week.

📡 PRESS RELEASE DECODER

What the press releases actually mean

Revolution Medicines Drops a Landmark Pancreatic Cancer Dataset — Then Raises $2 Billion Before the Ink Is Dry

📅 Date: April 13, 2026 | 🏢 Company: Revolution Medicines | 💊 Drug/Asset: Daraxonrasib (RMC-6236), multi-selective RAS(ON) inhibitor | 🏷️ Event Type: Phase 3 Data Readout

Revolution Medicines reported topline results from the Phase 3 RASolute 302 trial of daraxonrasib in previously treated metastatic pancreatic ductal adenocarcinoma (PDAC). Median overall survival was 13.2 months on daraxonrasib versus 6.7 months on standard chemotherapy — a hazard ratio of 0.40 (p<0.0001). The trial met all primary and key secondary endpoints, including PFS and OS in both the RAS G12 mutation population and the full intent-to-treat population. Safety was manageable with no new signals. intends to file an NDA under a Commissioner’s National Priority Voucher (CNPV) and will present detailed results at ASCO 2026. Two days later, the company priced a concurrent upsized offering: $1.5B in common stock at $142/share plus $500M in convertible notes due 2033 (0.50% coupon, ~40% conversion premium), totaling $2.0B in gross proceeds.

BPS Take: What an incredible data readout. KRAS was thought to be an untouchable target for the longest time, but the RVMD story is why it’s important for science to keep getting funded even in areas that seem too daunting. A 60% survival benefit in 2L pancreatic cancer, notoriously one of the most devastating and hard to treat cancers, is truly remarkable. No doubt about it, this drug is going to get the red carpet treatment all the way to approval. With the CNPV in tow, this might end up being one of the shortest FDA reviews ever.

Now for the business side of the equation. As of this writing, RVMD is sitting at roughly $31B market cap. Remember back in January, there were rumors swirling about AbbVie buying them (which never made sense, because I don’t think they had the cash) and Merck wanting to buy them (which made a ton of sense). RVMD wanted $30B at the time and there were only a couple companies who had the war chest to pull the trigger on something that big. With the lead asset now being pretty much entirely de-risked, the company sits at the very valuation the were looking for in January.

If we guesstimate (conservatively) $5B-$7B in peak sales for darax and consider its mostly de-risked and likely to have a strong launch, just darax alone gets you to anywhere between $25B - $35B in value before considering its platform and pipeline. Realistically a “fair” buyout number would have to be, I dunno, maybe $40B-$45B depending on how competitive a process it is? The reality is that that might be too big an acquisition for any Big Pharma to swallow, and I think the RVMD folks are telling you that they know that.

Within 48 hours of dropping the data, RVMD priced a $2B capital raise — upsized from the originally announced $1B. The proceeds are earmarked for general corporate purposes including commercial launch preparation and the four ongoing Phase 3 daraxonrasib programs (three in PDAC, one in NSCLC). This is a company that already had $500M coming from Royalty Pharma through a pre-approval funding deal signed in June 2025, and they’re now stacking another $2B on top. Rest assured, they are preparing to commercialize this drug themselves and grow into a BioPharma middleweight. I predicted RVMD would be bought in my acquisitions piece earlier in the year, but now I just don’t see it happening anymore. Instead, RVMD is going to grow and become a potential acquirer themselves, redeploying darax cash flows to continue buildout a strong pipeline of target anti-cancer treatments.

And guess what? This is good for the sector. Not every oncology darling that hits a home run needs to be swallowed up by the big fish. We’re seeing more deals from the mid-size players lately, which means more commercial scalers that can take small biotech’s innovations and deliver them to patients.

Allogene’s Big Swing Starts Paying Off: Cema-Cel MRD Data Clears Futility in First-Line DLBCL

📅 Date: April 13, 2026 | 🏥 Company: Allogene Therapeutics | 💊 Drug/Asset: Cemacabtagene ansegedleucel (cema-cel), allogeneic CD19 CAR-T | 📦 Event Type: Phase 3 Pivotal Interim Futility Analysis

Allogene reported data from the planned interim futility analysis of the pivotal Phase 2 ALPHA3 trial evaluating cema-cel as first-line consolidation therapy in high-risk large B-cell lymphoma (LBCL). At the protocol-defined cutoff (first 24 patients randomized, 12 per arm, Day 45 MRD assessment), 58.3% (7/12) of cema-cel patients achieved MRD negativity versus 16.7% (2/12) in the observation arm — a 41.6 percentage-point absolute difference, well above the 25-30% threshold Allogene considered clinically meaningful based on published literature. Plasma ctDNA dropped a median of 97.7% from baseline in the cema-cel arm versus a 26.6% median increase in the observation arm. Safety was clean: zero CRS, zero ICANS, zero GvHD, no treatment-related SAEs, and no treatment-related hospitalizations. Ten of twelve cema-cel patients were managed entirely outpatient. Community cancer centers — some with no prior CAR-T experience — accounted for approximately 33% of screening activity and infusions. The trial is enrolling across 60+ sites, targeting ~220 patients. Enrollment completion is expected by year-end 2027, with an interim EFS analysis anticipated mid-2027 and primary EFS in mid-2028.

Separately, Allogene priced a public offering on April 14 of 87.5M shares at $2.00/share, with the underwriters’ over allotment fully exercised, bringing the total raise to $200.4M in gross proceeds. The stock had spiked from the low $2s to $4.46 on the data release before the offering announcement pulled it back. At a market cap of roughly $660-740M, the dilution is significant — but the cash extends their runway to the primary EFS readout in mid-2028.

BPS Take: A lot of people have written off allo’ CAR-T. I get it, the technology has been “almost there” for years and the clinical track record has been spotty. But this company deserves enormous credit for the trial they chose to run. Every other allo’ CAR-T company targeting DLBCL went to the obvious, safe places: 3L+ post-CD19 CAR-T, then 2L but randomized against transplant, or pivoted into autoimmune disease. Allogene leapfrogged all of that and went straight to first-line consolidation — treating high-risk patients right after they finish frontline chemo, before they’ve relapsed, using MRD assessment as the guiding light. That’s a big risk, as they are both looking to move ahead of well-established auto’ CAR-T and also change the way DLBCL is treated.

The safety data here may actually be more important than the efficacy signal. The reason CAR-T has been stuck in academic medical centers is because of toxicity and logistics. CRS and ICANS can require ICU-level monitoring. Autologous manufacturing takes 3-6 weeks per patient. Cema-cel showed zero CRS, zero ICANS, outpatient management, and delivery at community centers with no prior CAR-T experience. If that holds, it removes two big barriers to CAR-T adoptions and enables allo’ CAR-T to compete in a community setting where very few auto’ CAR-Ts are even being administered.

The opportunity behind what Allogene is pushing is clear, but the road ahead is not without major hurdles. Neither MRD testing nor consolidation therapy are standard practice in LBCL today. However, of all types of docs, oncologists are some of the quickest to change when data supports it. The hard part is still ahead, event free survival is the real endpoint. While the early MRD data looks good, it is still just n=24 patients. But the directionality, combined with that safety profile, is exactly what the field needed to see to take allo’ CAR-T seriously again. As for the $200M raise at $2.00 — painful dilution, but it gets them to the pivotal readout. That’s the only thing that matters right now. It’s a bold strategy. Let’s see if it pays off for them.

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Replimune Lays Off 63 After Second FDA CRL for RP1; CEO Charges “The System Failed” Patients

📅 Date: April 13, 2026 (layoffs disclosed; CRL issued April 10) | 🏢 Company: Replimune | 💊 Drug/Asset: RP1 / vusolimogene oderparepvec + nivolumab | 🏷️ Event Type: CRL Consequence — Layoffs + Regulatory Flashpoint

THE FACTS:

Following the FDA issuing a second CRL last week, Replimune disclosed 63 layoffs via Massachusetts WARN filing effective through April 2026. CEO Sushil Patel publicly stated the company lacks sufficient cash to advance RP1 further without accelerated approval. Patel charged “the system failed” patients — framing the CRL as a regulatory policy failure, not a data failure. FDA’s CRL was publicly released under Commissioner Makary’s new real-time CRL transparency policy (part of a batch of 89 previously unpublished CRLs).The case sparked a WSJ opinion piece calling for FDA regulatory flexibility; a BioSpace analysis countered that many Americans actually support stricter FDA standards. Cash-constrained; path forward for RP1 without AA pathway highly uncertain

BPS’ Take: We discussed the CRL in last week’s LWTB, so I won’t rehash that analysis. It’s always painful to see layoffs in our sector, since we know how hard people work to actualize new scientific ideas. I’m hopeful the Replimune folks who are now without a home can find a new company to join soon. As for the CEO, I think his comments are a political move to point blame at an already controversial and disappointing FDA leadership team, and divert some blame for the fact that there were clear flaws in how data were collected in their study. I worry about the precedence this may set though. When Moderna’s flu vaccine was denied by this FDA, their CEO also took to the media to point the blame at regulators. It may honestly be warranted, given how capricious this FDA has been, but I hope this is just a one-term thing and we don’t get int he habit of playing politics and Spin City with the FDA. Drugs have a better chance of getting approved when industry and regulators can work constructively with one another.

🌐 CONNECTING THE DOTS

When the outside world meets biopharma

Big Tech Moves Into the Lab — And Big Pharma Moves Into Big Tech

📅 Date: April 14-16, 2026 | 🏥 Companies: Novartis / Anthropic, Novo Nordisk / OpenAI, Amazon Web Services | 💊 Topic: AI-Pharma Convergence | 📦 Event Type: Board Appointment, Strategic Partnership, Platform Launch

Three stories dropped this week symbolizing the convergence between BioPharma and Tech worlds.

Novartis CEO Vas Narasimhan joined Anthropic’s board of directors on April 14. Anthropic is the developer of the Claude AI model and describes itself as an AI safety and research company. Narasimhan said in a statement that “AI is accelerating solutions to some of the hardest scientific challenges, from deepening our understanding of disease biology to designing better medicines.” Novartis has existing AI partnerships with Alphabet’s Isomorphic Labs (AlphaFold-based small molecule discovery), Schrödinger, Generate:Biomedicines, and Relation Therapeutics. Narasimhan has publicly stated Novartis’s goal of halving the target-to-clinic timeline from four years to two. The appointment comes while the Trump administration has banned Anthropic’s Claude across the federal government, including HHS. Novartis declined to comment on potential political repercussions.

Novo Nordisk announced a strategic partnership with OpenAI to integrate AI across discovery, manufacturing, and commercial operations. Initial pilots are underway across R&D, manufacturing, and commercial units, with broader rollout planned through 2026. The partnership includes workforce training programs to increase AI literacy across Novo’s global organization. Novo’s existing AI partnerships include Valo Health (up to 20 programs in obesity, T2D, and CV disease), NVIDIA and Denmark’s DCAI (sovereign AI supercomputer for drug discovery), and Microsoft Research (internal AI platform for research, regulatory, and trial design). OpenAI has also signed pharma collaborations with Sanofi/Formation Bio, Thermo Fisher, Moderna, and Eli Lilly.

Amazon Web Services launched Amazon Bio Discovery (ABD), a drug discovery platform integrating 40+ AI biological foundation models with wet-lab CRO partners (Ginkgo Bioworks, Twist Bioscience, A-Alpha Bio). The platform uses a four-stage “lab-in-the-loop” process: in silico workflow building, assistant-led experimental design, computational result analysis, and transfer of top candidates to CRO wet labs for validation. Users can access the AI model library, upload custom models, or use third-party tools. ABD is being tested at Bayer, the Broad Institute, Voyager Therapeutics, and Memorial Sloan Kettering, where a project generated 100,000 antibody candidates sent for wet-lab testing in a matter of weeks. AWS currently provides cloud services to 19 of the top 20 pharma companies.

BPS Take: BioPharma wants to integrate AI/Tech just as much as AI/Tech wants to integrate into BioPharma. It could end up being quite a fruitful partnership if done right. As I’ve written in a past post, I worry about the tech folks hijacking the messaging in this convergence space, as they have a tendency to overpromise and underdeliver. Having someone like Narasimhan on the board of the “ethical AI company” may limit some of that hype speak. Of all the Big Pharma CEOs I think he and Dave Ricks from Lilly are probably the two best communicators, so it’s a sharp pick by Anthropic.

From the Tech/AI side, this continues down a trend of moving into hard/deep tech sort of spaces where AI can add more value in the long-run. The end of most enterprise software may be within view given how quickly AI coding agents have progressed. To meet the trillion dollar valuations some of these AI companies hold, they’ll need to apply the intelligence they are developing to harder to solve problems, like biology. What I would like to see the investors and journalists do is keep both the Big Pharma companies and AI companies accountable on metrics of progress when these sorts of deals/launches are announced. I hope some junior equity analyst and JP Morgan checks in a year from now with Novo’s CEO and asks them to show how their partnership with OpenAI has materially and countably added value to Novo’s business. There is clear upside to be had in making our drug companies more AI-native, but I imagine more of these deals will happen, and we need to know which ones are working and which ones aren’t and why. If we’re going to really enable AI to help us make progress building the next generation of new drugs, these BioPharma-AI partnerships need to be held to a higher standard or else they just become a “cool” press release.

RFK’s Peptide Push: Removing Safety Guardrails Is Not the Same as “Restoring Access”

📅 Date: April 2026 | 🏥 Agency: HHS / FDA | 💊 Topic: Category 2 Peptide Reclassification (BPC-157, Thymosin beta-4 fragment, Melanotan II, Ibutamoren, 8 others) | 📦 Event Type: Regulatory / Policy Action

HHS Secretary Robert F. Kennedy Jr. announced that 12 peptides will be removed from the FDA’s Category 2 list (”Bulk Drug Substances that Raise Significant Safety Risks”) after nominators withdrew them. The affected substances include BPC-157, Thymosin beta-4 fragment (LKKTETQ), Epitalon, GHK-Cu (injectable), MOTS-c, DSIP (Emideltide), Dihexa Acetate, Ibutamoren Mesylate, Melanotan II, KPV, Semax, and Cathelicidin LL-37. The peptides will be brought before the Pharmacy Compounding Advisory Committee (PCAC) at its next two meetings beginning in July for evaluation. Kennedy framed the move as “restoring regulated access” and shifting demand away from a black market that emerged after the Biden FDA placed these substances in Category 2 in September 2023.

The framing requires context. Removing peptides from Category 2 does not place them on Category 1 (substances eligible for compounding). There needs to be a committee ruling and/or new FDA regulatory action to formally place these peptides on the Category 1 list. Each substance will require efficacy data and clinical justification before PCAC. The most prominent substance on the list, BPC-157, has been aggressively marketed for tissue repair, gut health, and recovery in wellness circles, but the human evidence base is effectively nonexistent. Nearly all published data comes from animal studies, predominantly from a single research group. There are no completed randomized controlled trials in humans. Other compounds on the list include Melanotan II (a tanning peptide with case reports of melanoma promotion), Ibutamoren (a growth hormone secretagogue with insulin resistance concerns), and Dihexa (a cognitive-enhancement peptide with minimal human safety data).

BPS Take: There’s a legitimate argument that the 2023 Category 2 action was handled clumsily and did push some demand to unregulated black markets. That part of Kennedy’s framing is fair. However, the solution to bad regulation is better regulation, not removal of safety guardrails under the banner of “following the science.” The irony of that phrase here is thick, given that the science for most of these peptides in humans barely exists. The PCAC review is the right next step, but only if it’s conducted with actual clinical rigor and not predetermined political outcomes. If you’re a patient considering these compounds, understand that “removed from the danger list” does not mean “proven safe and effective.” Category 2 removal is not Category 1 approval. These substances still lack the clinical evidence that every other drug approved in the US is required to produce before reaching patients.

💰 FOLLOW THE MONEY

Deals, dollars, and what they signal

UCB Acquires Neurona Therapeutics for Up to $1.15 Billion, Making a Generational Bet on Interneuron Cell Therapy for Drug-Resistant Epilepsy

📅 Date: April 17, 2026 | 🏢 Company: UCB / Neurona Therapeutics | 💊 Drug/Asset: NRTX-1001, GABAergic interneuron cell therapy (stem-cell derived) | 🏷️ Event Type: M&A Acquisition

UCB announced an agreement to acquire privately held Neurona Therapeutics for $650 million upfront plus up to $500 million in development and commercial milestones, totaling up to $1.15 billion. The deal is expected to close by end of Q2 2026. The acquired asset is NRTX-1001 — a GABAergic interneuron cell therapy derived from pluripotent stem cells, designed as a one-time surgical implant for patients with drug-resistant focal epilepsy. The specific indication in clinical development is drug-resistant mesial temporal lobe epilepsy (mTLE), both unilateral and bilateral, with and without mesial temporal sclerosis (MTS). In a clinical update released April 8, Neurona reported Phase 1/2 data showing a 92% median reduction in disabling seizures during the efficacy endpoint period. The mechanism involves transplanting stem cell-derived GABAergic interneurons into seizure-generating brain regions to restore long-term inhibitory GABA tone — a one-time intervention concept targeting the underlying interneuron deficit in drug-resistant epilepsy. UCB framed the deal as a strategic expansion into regenerative medicine, building on its 30-year heritage in epilepsy (Vimpat, Briviact).

BPS Take: Hey hey! How about that?! A Cell Therapy acquisition! Not quite the CAR/TCR-T deals of the past, but folks like me who wear the battle scars from this world should rejoice.

It’s easy to forget how big a company UCB is. They sit at roughly $59B and are a rather quiet middleweight. This deal fits right into UCB’s epilepsy specialty, an area that really does not have a ton of major players focusing-in on it (Eisai and Jazz come to mind). UCB now has a potentially curative approach to go alongside many more chronic treatments it offers, like VIMPAT and BRIVIACT that face generic erosion. UCB is probably coming to terms with how marketing this drug probably changes their business model a bit. The NRTX-1001 cells require a surgery to implant and a robust cell therapy manufacturing infrastructure after all. Epilepsy is an interesting area in drug development too, as you compete with many med device options (mostly implants) that look to combat seizures as well. This will be an interesting one to follow in terms of price and launch as UCB gets going with the commercial roll out.

Kailera Therapeutics Prices $625M IPO — Largest-Ever US Biopharma IPO — Surges 63% on Day One

📅 Date: April 16-17, 2026 | 🏢 Company: Kailera Therapeutics | 💊 Drug/Asset: Ribupatide (KAI-9531), GLP-1/GIP injectable dual agonist (Phase 3) + oral GLP-1 pipeline | 🏷️ Event Type: IPO / Financing

Kailera Therapeutics priced its IPO at $16 per share, upsized from an initial $500M target to approximately 39.1 million shares for gross proceeds of $625 million — confirmed as the largest-ever US biopharma IPO by gross proceeds at pricing, surpassing Moderna’s 2018 record of $604 million. The stock surged 63% on its first day of trading on April 17, 2026, listed on Nasdaq under ticker KLRA. The company is led by CEO Ron Renaud, who previously led Idenix Pharmaceuticals, Translate Bio, and Cerevel Therapeutics. Kailera’s pipeline consists of clinical-stage obesity assets in-licensed from Hengrui Pharma (Shanghai). The lead asset, ribupatide, is an injectable GLP-1/GIP dual agonist currently in a global Phase 3 trial for obesity, with results expected in 2028. A second program, oral ribupatide, is in Phase 2b with results expected in 2027. Expected close of the offering is April 20, 2026.

BPS Take: This company is a classic China arbitrage play. There doing what Summit Therapeutics is doing with PD-1xVEGF, but for GLP-1s. However, unlike Summit, Kailera isn’t the first-comer to GLP-1s. They enter this space, with many other Big Pharma heavyweights already approved or in parallel Phase 3 studies. Given the current geopolitical environment (tariffs, China pharma scrutiny), how does this origin story affect long-term regulatory, IP, and commercial risk? Can a $625M Phase 3 obesity play compete with Novo and Lilly’s established commercial infrastructure, manufacturing scale, and brand recognition? It’s still not clear what their differentiation is vs. the market leader(s). Perhaps their oral GLP-1 nets out a superior product profile to the current offerings? It’s clear from the early sales data that customers prefer orals to injectables.

Nonetheless a $625M for a fast-follower GLP-1 approach may be the going rate for this market. We just aren’t used to seeing that big a numbers associate with a fast-follower. Kailera has three Phase 3 studies for KAI-9531 set to readout in 2028. I think we are very quickly approached peak-GLP-1, with many of the players who are committed to this space already having asset(s) in their pipeline. The “out” for Kailera might be dependent on existing programs from the Big Pharmas yet to launch in Obesity (e.g. Regeneron, Pfizer, Amgen, Roche, AstraZeneca etc.) running into hurdles, forcing them to look elsewhere to buy a backbone GLP-1 asset. Then again, Big Pharmas do get itchy trigger fingers, and if it starts to look like Kailera could accelerate someone’s time-to-market in the massive Obesity/T2DM space, one of that group could look to acquire them to “cut the line”.

🚨WEEKEND DEAL: Eli Lilly in Advanced Talks to Acquire Kelonia Therapeutics for >$2 Billion

📅 Date: April 19, 2026 (rumored, per WSJ/Reuters) 🏢 Acquirer: Eli Lilly ($LLY) → Target: Kelonia Therapeutics (private) 💰 Deal value: >$2 billion (structure TBD) 💊 Lead program: KLN-1010 — in vivo BCMA-directed CAR-T for relapsed/refractory multiple myeloma (Phase 1, inMMyCAR study) 🏷️ Event Type: rumored acquisition

Kelonia Therapeutics is a private biotech built around its iGPS® (in vivo Gene Programming and Stealthing) platform, which uses an engineered lentiviral vector particle with envelope modifications to generate CAR-T cells directly inside the patient’s body — bypassing the need for leukapheresis, ex vivo manufacturing, and lymphodepletion that define conventional CAR-T therapy. The lead program KLN-1010 targets BCMA on multiple myeloma cells and is the first anti-BCMA in vivo CAR-T program studied in a multi-center clinical trial. At ASH 2025 (Dec 9), Kelonia presented first-in-human data from the Phase 1 inMMyCAR study showing that all four dosed patients achieved MRD-negative responses, with CAR-T cells detected in both bone marrow and peripheral blood through month 3, predominantly composed of memory-phenotype T cells. No lymphodepletion chemotherapy was required. Treatment turnaround from consent to dosing was 13-18 days.

If the deal closes, it would be Lilly’s second in vivo CAR-T acquisition in 2026 following its $2.4 billion purchase of Orna Therapeutics (announced Feb 9, 2026). The two platforms are complementary: Orna uses LNP-delivered circular RNA to generate CAR-T cells transiently, positioned for autoimmune indications where temporary B-cell depletion may be sufficient; Kelonia uses lentiviral DNA integration for durable CAR-T cell persistence, positioned for hematologic malignancies and oncology where lasting anti-tumor immunity is required. Together, the two acquisitions would give Lilly both transient (RNA) and durable (DNA) in vivo CAR-T modalities across autoimmune and oncology.

The deal would also directly affect J&J, which signed a strategic in vivo CAR-T discovery collaboration with Kelonia in November 2025 and is already the dominant ex vivo CAR-T franchise holder via Carvykti (ciltacabtagene autoleucel).

UPDATE: Lilly announced that they have agreed to acquire Kelonia for $3.25B upfront plus up to an additional $3.75B in milestones.

BPS’ Take: $LLY is clearly signaling belief in in vivo CAR-T writ-large. With Orna (LNP/RNA-based) for autoimmune and now Kelonia (LVV/DNA-based) for heme/onc, Lilly is assembling both halves of the in vivo CAR-T toolkit from a position of strength afforded by GLP-1 cash flows. This is another low-risk/high-reward bet on novel science — the kind of deal Lilly can make when you’re generating the revenue they are and don’t have immediate pressure to fill patent cliffs. I called the Kelonia acquisition in my predictions post earlier this year. The J&J folks have to be disappointed if they lose out to Lilly on this one. J&J having an in vivo CAR-T play in Multiple Myeloma might be too important for them to let Lilly have Kelonia without a bidding war.

In vivo CAR-T has quickly become one of the most competitive spaces across Big Pharma players, despite little clinical maturity. Whose platform(s) will win? Differentiation between the multitude of companies in this space has largely been theoretical to date without substantive clinical data — but Kelonia’s 100% MRD-negativity rate in the inMMyCAR study, without lymphodepletion, is the kind of signal that makes a >$2B price tag look like a bargain if it holds up in larger cohorts.

Update: With the full deal terms now disclosed, you are seeing Lilly really throw around its weight. $3B+ for roughly 4 patients worth of data is pretty incredible. I would assume Lilly has seen more under confidentiality. Still, it resets the market for future in vivo CAR-T deals. The plethora of other players in this space have to be happy seeing the price tag. For Lilly, this is still chump change. ZEPBOUND alone did $4B+ in revenue in Q4’25, and perhaps that could even double at some point. They’re playing in a different ballpark than any of their peers. You have to believe JNJ at least got a call about this deal and put in an offer. Up to $7B was likely too rich for them. Their saving grace might be the fact that their T-cell engager data in multiple myeloma is so good and they’ve raised the bar so high in that field, that perhaps in vivo CAR-T struggles to meaningfully surpass the efficacy thresholds they’ve set. Only time will tell.

Back next week with another edition of LWTB! Stay tuned and hope you have a strong start to your week!

The GLP-1 field is off like a rocket ship and is highly competitive. Atop the leaderboard, sits Eli Lilly , the most valuable healthcare company in the world. They got there largely on the backs of the performance and potential of three products:

• tirzepatide: Lilly’s once-weekly GLP-1/GIP agonist that quickly displaced Novo’s semaglutide as the market leader.

• orforglipron: Lilly’s small-molecule oral GLP-1 offering market-leading convenience and strategically advantageous pricing flexibility.

• retatrutide: Lilly’s triple agonist (GLP-1/GIP/GCG) that is shattering the upper limit of weight loss that can be achieved by pharmacotherapy.

Perhaps little known to some, Lilly actually has a fourth GLP-1 based molecule in late-stage studies, called brenipatide. It has 14 active clinical trials, is targeting enrollment of almost 5,000 patients, but gets almost no mainstream coverage. However, when we look at where, how, and why Lily is developing brenipatide, we might come to see it as its most important GLP-1 offering yet.

Where it is different

Brenipatide, as far as I can tell, doesn’t have anything super special to it other than it is sort of a long-acting version of tirzepatide. Just like ZEPBOUND (tirzepatide), it’s a dual GLP-1/GIP receptor agonist and a peptide-based biologic that requires a subcutaneous injection, but instead of once-a-week dosing, it’s once-monthly dosing.

Beyond that, perhaps the most interesting aspect of brenipatide is its clinical development plan. Whereas Lily’s three other leading GLP-1-based programs are largely all focused on cardiovascular and metabolic indications (with some exceptions), brenipatide is unique in its development plan, which focuses largely on addiction, neuropsychiatry, and respiratory disease. If successful, it would expand GLP-1 treatment into an an entirely new therapeutic frontier.

Explore My Consulting Work

Looking at a breakdown of the larger studies , we can get a sense of both what Lilly’s strategy is with this molecule as well as where they see the highest level of confidence.

Read more

We’re back for the third edition of Last Week Tonight in BioPharma (LWTB)!

In case you’re new, here is what I am trying to do with this series:

1. A short recap of the most interesting stories from the past week with strategic insights to get you ready for your Monday meetings.

2. Up to 3 key events per category:

   • Press Release Decoder: going beyond the company speak, reading between the lines, thinking about what isn’t being said, to illustrate the strategic implications of a company’s moves that don’t make it into the press release

   • Connecting the Dots: looking at stories that are either about the macro or from the mainstream news and how they may impact BioPharma

   • Follow the Money: quick takes on some key deals that were struck and what they mean for those companies, their competitors, or the sector at-large

3. Free to all subscriber levels! Although if you like my free content and have $8/month to spare (or expense to your company), I think you’ll love the deeper analyses my paid subscribers get. You can upgrade at any time by clicking the button below.

   Subscribe now

And with that, let’s get into what happened this past week.

📡 PRESS RELEASE DECODER

What the press releases actually mean

Replimune's RP1 Receives a Second FDA Complete Response Letter — And This Time, It Looks Terminal

Source: FDA / Replimune IR | Date: April 10, 2026

The FDA issued a second CRL for Replimune's BLA for RP1 (vusolimogene oderparepvec) in combination with nivolumab for adult patients with advanced melanoma who progressed on anti-PD-1 therapy. The new CRL was reviewed by an entirely different clinical review team than the first — assembled specifically to "maintain objectivity" — and that team unanimously concluded the data are insufficient to demonstrate substantial evidence of effectiveness. The FDA cited inability to isolate RP1's contribution when combined with nivolumab, heterogeneity of the IGNYTE trial population, unreliable response assessments (including the finding that 53% of responders had no non-injected target lesions to assess systemic activity), and the inadequacy of the resubmission package, which included an unplanned interim look at just 40 patients from the ongoing Phase 3 RP1-104 trial (10% of planned enrollment). Replimune's press release struck a combative tone, accusing the FDA of "inconsistent communication and a fragmented and slow-moving regulatory process," announcing substantial layoffs and the scaling back of US manufacturing operations, and stating that "without timely accelerated approval, the development of RP1 will not be viable."

BPS’ Take: I spent a lot of time reading the actual CRL and Replimune’s response side by side, and this situation is genuinely more complicated than either side is letting on. Kenny and I discussed the Replimune situation in detail during an old podcast episode (link). My take then was that this FDA was pulling the rug out from under them and unfairly blocking an important new medicine from being available to late-stage melanoma patients. Now I’m not so sure who is right, but I am very certain both the FDA and Replimune are obscuring the truth, which is a bad look for all parties involved.

The FDA’s scientific case on response assessment integrity is strong. When over half of your responders had all their target lesions injected with the virus that’s a fundamental interpretability problem. Add the confounding from surgical excisions of target lesions before response assessments and re-injection of enlarging tumors before independent review could call progression, and the reported 33% ORR may be artificially inflated. Replimune did a sub-par job maintaining high standards of data quality when running their study. That to me seems pretty clear.

But Replimune’s process complaints also have teeth. They claim a senior member of the original review team publicly stated that the clinical team believed the data supported contribution of effect, but leadership disagreed. If that’s true, assembling a “new” review team to ensure “objectivity” looks less like good regulatory practice and more like opinion shopping. Replimune also claims the FDA acknowledged at the September 2025 Type A meeting that randomizing patients to anti-PD-1 alone was not feasible and didn’t raise further heterogeneity concerns after melanoma expert testimony, only to resurrect both issues in this CRL. And they say they submitted data based on an FDA suggestion, asked for feedback, received none, had the resubmission accepted as a “complete response,” and then got rejected on the very approach they were told to pursue. Add to all this that the drug received breakthrough therapy designation, but also in 2021 the FDA said they recommended a control arm, and it makes for a really confusing story.

The contribution-of-effect argument is where I have the most sympathy for Replimune. Every one of these patients had already failed anti-PD-1 therapy. The expected response rate to nivolumab re-challenge in this population is about 6-7%. IGNYTE showed ~33%. You don’t need a randomized control to know nivolumab alone isn’t generating that response. The “failed A, now give A+B” paradigm is well-established in oncology. I think it would be different story if the FDA requested an RP-1 monotherapy arm, but that doesn’t really seem to be the case.

Where does this leave things? Replimune is essentially signaling that the program (and perhaps their company) is dead. This is a bad outcome for melanoma patients who have limited options after PD-1 failure, perhaps at least one nail in the oncolytic virus field (at least for a little bit), a cautionary tale about the risks of pursuing accelerated approval on a single-arm combination study without a concurrent control, and a warning not to make enemies with the FDA. Industry and regulators need to work collaboratively. That’s how new drugs have the best chance of getting approved even when evidence is imperfect.

Lessons for me? I think despite the improvement this FDA has made in CRL transparency, we the public, still aren’t getting a full enough story to adjudicate blame when these situations arise. I could have done a better job considering the posibility that Replimune managed their study poorly, which played into the CRLs.

🌐 CONNECTING THE DOTS

When the outside world meets biopharma

Ben Sasse, Pancreatic Cancer, and the Harsh Reality of Novel Cancer Treatment

Source: New York Times Opinion | Date: April 9, 2026

The New York Times published a profile of former Nebraska Senator Ben Sasse, who announced in December 2025 that he has Stage 4 metastatic pancreatic cancer. The piece — an edited transcript of an interview on the "Interesting Times" podcast — chronicles Sasse's reflections on mortality, family, faith, and living with a disease he bluntly called "a death sentence." Sasse is 53 years old. In the interview he reveals he is taking daraxonrisib, Revolution Medicine’s pan-RAS(ON) inhibitor that was the reason for many buyout rumors a few months back. Sasse also bares openly a bloody face in the interview, a result of the drugs on-target AE profile.

BPS’ Take: Pancreatic cancer has a five-year relative survival rate of 13%. For Stage 4 disease specifically, it drops into the single digits. Luckily daraxonrasib has shown promising signals in this setting, where many past drugs have failed. It’s probably not going to cure Sasse, but it is a tremendous step up in life extension compared to the slew of chemo and radiation that is standard of care. The interview is also a great reminder of how much patients can still suffer despite their cancers shrinking. Bleeding from the face, nausea, dependency on morphine - all of that adds to the physical tole of fighting cancer and is a reminder of how much further we still have left to go in conquering this family of diseases.

FDA Proposes Clinical Trial Notification Pathway — Makary’s Biggest Structural Reform Yet

Source: FDA FY2027 Budget Proposal / BioSpace / RAPS | Date: April 3-8, 2026

The FDA, as part of its FY2027 budget proposal released the week of April 3, included a legislative request to create a new “Clinical Trial Notification Pathway” as an alternative to the existing Investigational New Drug (IND) application process. The current IND system requires sponsors to compile extensive toxicology, pharmacology, and manufacturing data before initiating first-in-human trials, triggering a mandatory 30-day FDA review hold. The proposed new pathway would create an expedited alternative for Phase 1 programs where adequate preclinical data already exists, modeled in part on Australia’s Clinical Trial Notification system that delegates scientific and ethical review to local committees rather than requiring national regulator sign-off before trials begin. FDA Commissioner Marty Makary framed the proposal as part of the agency’s transition “from a reactionary system to a proactive system,” citing concerns that the current regulatory burden is driving early-stage clinical trials overseas — particularly to China, which has been attracting early-phase research through its own decentralized trial system and lower labor costs.

BPS’ Take: This is potentially the most consequential structural reform Makary has proposed since taking over the FDA. More than releasing the CRLs and more than the 2-month PRV. If implemented, a Clinical Trial Notification pathway would fundamentally change the speed and economics of Phase 1 development in the US.

The Australia comparison is apt. The Australian CTN system is a major reason why companies like to run early-phase work down under. You can get into clinic weeks faster and get clinical proof-of-concept that much sooner. Makary is essentially arguing that if we don’t create a competitive alternative here, the US will keep hemorrhaging early-stage trial activity to jurisdictions with faster regulatory onramps (notably China). Chinese clinical trial volume, especially for testing novel drugs in Phase 1, has exceeded the US by some measures. This is driven in part by cost advantages but also a more streamlined early-phase regulatory process.

This change would be a big boost to the entire AI for Drug Development field too, as it would speed up the rate it which novel biology could be tested in humans, speeding up the data (and increasing the quality of data) that could feed into AI platforms.

Where this may get hung up is that it requires Congressional legislation. That means it has to survive the appropriations process, potential industry lobbying (some large pharma companies could benefit from the IND burden because it raises barriers to entry for competitors), and whatever political dynamics are at play by the time this hits the floor. Hopefully the anti-China competitive argument is sufficient enough to push this through, as it would benefit innovation significantly over the long run.

💰 FOLLOW THE MONEY

Deals, dollars, and what they signal

Gilead Acquires Tubulis for Up to $5B — ADC Platform Play Gets Aggressive

Source: Gilead Sciences Press Release / Reuters / STAT News | Date: April 7, 2026

Gilead Sciences announced a definitive agreement to acquire Tubulis GmbH, a Munich-based clinical-stage ADC company, for $3.15 billion upfront in cash plus up to $1.85 billion in contingent milestone payments. Tubulis’ lead asset is TUB-040, a NaPi2b-directed topoisomerase-I inhibitor ADC currently in Phase 1b/2 for platinum-resistant ovarian cancer and non-small cell lung cancer. The company also brings TUB-030, a 5T4-targeted ADC with early clinical data in solid tumors, and a proprietary conjugation platform featuring its Tubutecan linker-payload technology designed to improve ADC therapeutic index. The deal follows a two-year collaboration between the companies and builds on Gilead’s oncology transformation through prior acquisitions of Immunomedics (Trodelvy) and Kite (cell therapy). Tubulis will operate as a dedicated ADC research organization within Gilead, with Munich serving as a hub for ADC innovation. The transaction is expected to close Q2 2026.

BPS’ Take: Gilead is buying time and technology simultaneously. Trodelvy faces growing competition from the AstraZeneca/Daiichi Sankyo Enhertu partnership and a wave of next-gen ADCs. Tubulis’ conjugation technology — specifically the Tubutecan linker-payload system — is the kind of platform asset that could generate compounding value. Its lead asset is focused on Napi2b, a once failed target (i.e Mersana), but the dollar signs associated with this deal signal that this ADC format may be meaningfully differentiated than its predecessors. With the $3.15B upfront for a company with one asset in Phase 1b/2, but a differentiated platform behind it, Gilead is signaling that they both believe in Tubulis’ lead compound and are ready to discover and develop their own ADCs moving forward. AstraZeneca proved that owning an ADC platform (via the Daiichi Sankyo partnership) creates compounding value across tumor types and Gilead is trying to do the same. However, sometimes you buy things thinking they are a platform company and they just turn out to be a pipeline-in-a-product company. We’ll see where this one ends up.

I found it interesting that Gilead felt the need to host a call to discuss this acquisition as well as the previous Arcellx and Ouros deals all in one, as all these deals were relatively spread out in time and not all that huge (by Gilead standards). In any case, you are seeing a clear coloring-in of the lines for what programs Gilead envisions carrying its revenues into the future, outside of its HIV powerhouse. They are going to be anchored in Cell Therapy for heme/onc, ADCs for solid tumors, and B-cell depletion for auto-immune disease, with optionality on other modalities coming from existing partnerships.

Neurocrine Acquires Soleno Therapeutics for $2.9B — A Rare Disease Bet With an EMA-Shaped Asterisk

Source: Neurocrine IR / Soleno IR / STAT News / BioPharma Dive / Reuters | Date: April 6-7, 2026

Neurocrine Biosciences announced the acquisition of Soleno Therapeutics for $53.00 per share in cash, approximately $2.9 billion total, to gain control of Vykat XR (diazoxide choline controlled-release) — the first and only FDA-approved treatment for hyperphagia in Prader-Willi syndrome (PWS). Vykat XR received FDA approval in March 2025 and launched commercially in Q2 2025, generating $190 million in early sales. PWS is a severe rare genetic disorder affecting approximately 400,000 patients globally and an estimated 20,000-30,000 in the US. The deal announcement on April 6 was followed the next day by Reuters reporting that Neurocrine and Soleno had jointly withdrawn the EMA marketing authorization application for Vykat XR in Europe, citing a request for additional data from European regulators. An EMA decision had originally been expected in mid-2026.

BPS’ Take: It’s rare to see smaller mid-size biotech do late-stage acquisitions like this, but I think more of these are healthy for the sector. It can’t just be the Big Pharmas doing all the acquisitions. We’ve seen the “middleweight” to “welterweight” class start do more deals as of late. Biogen last week, GenMab acquiring Merus, Biomarin acquiring Amicus, and Servier acquiring Day One. These are all commercial stage companies who are now operating like mini-Big Pharmas, using their cash flows to acquire late stage assets that boost their future inline revenues. Very interesting!

Vykat XR is the only game in town in Prader-Willi syndrome and has had a strong first months of launch. Competitor drugs, like that from Aardvark, have seemingly stalled, so their is clear runway here for Vykat XR to establish a meaningful commercial lead. The sales trajectory suggests there is a lot more upside to be had and the drug fits nicely into Neurocrine’s rare disease commercial infrastructure (Ingrezza in tardive dyskinesia, Crenessity in congenital adrenal hyperplasia).

The EMA market application withdrawal is a bit odd, especially when Europe is a major market. The deal math works if Vykat XR establishes itself as the undisputed standard of care for PWS hyperphagia in the US, but the European situation is a material overhang. I’d want to understand the specific nature of the EMA’s data request before calling this a clean win. Does Neurocrine think its better to punt on Europe entirely or is there more to the story?

Back next week with another edition of LWTB! Stay tuned and hope you have a strong start to your week!

We’re back for the second edition of Last Week Tonight in BioPharma (LWTB)!

ICYMI, here is what I am trying to do with this series:

1. A short recap of the most interesting stories from the past week with strategic insights to get you ready for your Monday meetings.

2. Up to 3 key events per category:

   • Press Release Decoder: going beyond the company speak, reading between the lines, thinking about what isn’t being said, to illustrate the strategic implications of a company’s moves that don’t make it into the press release

   • Connecting the Dots: looking at stories that are either about the macro or from the mainstream news and how they may impact BioPharma

   • Follow the Money: quick takes on some key deals that were struck and what they mean for those companies, their competitors, or the sector at-large

3. Free to all subscriber levels! Although if you like my free content and have $8/month to spare (or expense to your company), I think you’ll love the deeper analyses my paid subscribers get. You can upgrade at any time by clicking the button below.

   Subscribe now

And with that, let’s get into what happened this past week.

📡 PRESS RELEASE DECODER

What the press releases actually mean

Eli Lilly’s Foundayo (Orforglipron) Becomes First Oral Small-Molecule GLP-1 Agonist Approved for Obesity

Source: STAT News | Date: April 1, 2026

The FDA approved Foundayo (orforglipron) on April 1, 2026, making it the first oral small-molecule GLP-1 receptor agonist cleared for obesity and overweight in adults — a milestone that reshapes the multi-billion dollar weight-loss drug market. Phase 3 trials demonstrated 11.2–15% body weight reduction over 36–72 weeks; the drug carries a boxed warning for thyroid C-cell tumor risk but requires no food or water restrictions unlike Novo Nordisk’s oral semaglutide. Lilly priced the lowest dose at $149/month through LillyDirect with launch availability beginning April 6, positioning it as a direct cash-market competitor to Novo’s oral Wegovy subscription at $249/month, which launched the day prior.

BPS’ Take: My guy Ashwin, who runs GLP-1 Digest, sent out a sharp note about FOUNDAYO vs. Oral WEGOVY, breaking down the channel-specific price difference, and why Lilly comes out ahead, even though their efficacy numbers are nominally lower (which I agree with).

Strategically, this approval might trigger an oral GLP-1 price war with massive downstream implications for pharmacy channel economics, telehealth platforms, and Novo Nordisk’s market share. The big thing Lilly has working in its favor over Novo is the small molecule chemistry that goes into FOUNDAYO. It can be made far more inexpensively than oral WEGOVY, giving Lilly far greater gross margins to play with in a price war. If it becomes a game of limbo and we are asking “how low can you go?”, Lilly has far more proverbial lower back flexibility than Novo or any other oral peptide that looks to enter the market. Over the long-term, I think GLP-1s moving into their small-molecule oral era will bring down costs for patients, improve access, and overall make a lot of people a lot healthier.

Merck’s Enlicitide Decanoate Hits Phase 3 with 64.6% LDL Reduction — NDA Filing Set for April 2026

Source: Merck Investor Relations | Date: March 31, 2026

Merck’s enlicitide decanoate, the first oral PCSK9 inhibitor designed to deliver antibody-class LDL-lowering efficacy, met its Phase 3 primary endpoint at ACC.26 (March 28–29), demonstrating a 64.6% reduction in LDL-C from baseline versus guideline-recommended non-statin oral comparators — a magnitude of effect previously achievable only with injectable monoclonal antibodies like evolocumab or alirocumab. Merck plans to submit its NDA in April 2026, with the FDA having already awarded the drug a Commissioner’s National Priority Voucher in December 2025 to accelerate the review timeline. The oral formulation targets the enormous unmet need in cardiovascular patients who remain poorly adherent to injectable PCSK9 inhibitors despite proven mortality benefit.

BPS’ Take: An oral drug achieving 60%+ LDL reduction would fundamentally change the PCSK9 inhibitor market by solving the adherence problem that has suppressed penetration of REPATHA and PRALUENT, potentially unlocking a patient population orders of magnitude larger than what injectables have captured. It’s easy to forget that PCSK9 antibodies have been on market since 2015 and garnered peak sales of (only) ~$2B for what is a MASSIVE market. A lot of people have high cholesterol and with the updated ACC/AHA guidelines now including more aggressive targets for higher-risk groups, we could see an influx of patients on oral PCSK9 inhibitor therapy in short order.

🌐 CONNECTING THE DOTS

When the outside world meets biopharma

🚨 FRIDAY DUMP — Major regulatory/trade risk event: 100% import tariffs imposed on non-exempt branded pharmaceuticals, creating bifurcated competitive landscape

Trump Signs 100% Pharma Tariff Executive Order — 16 Large Pharma Companies Exempt After MFN Deals

Source: BioPharma Dive / STAT News / CNBC | Date: April 2, 2026

President Trump signed an executive order on April 2, 2026 under Section 232 authority imposing 100% tariffs on imported patented pharmaceuticals; generics and biosimilars are fully exempt, and EU, Japan, Korea, Switzerland, and Liechtenstein face a reduced 15% rate, while 16 large drugmakers — including Pfizer, J&J, AstraZeneca, Novo Nordisk, Eli Lilly, AbbVie, BMS, Gilead, Merck, Roche, Novartis, Amgen, Sanofi, GSK, Boehringer Ingelheim, and EMD Serono — are fully exempt having already signed most-favored-nation pricing agreements and committed to $400 billion in U.S. manufacturing investments. Companies that have not signed MFN deals can reduce their tariff burden to 20% by pledging domestic onshoring; tariffs take effect in 120 days for large companies and 180 days for smaller ones. PhRMA president Stephen Ubl stated the order “undermines U.S. biopharmaceutical leadership.”

BPS’ Take: This executive order creates an unprecedented two-tier competitive dynamic in U.S. pharma, with exempt incumbents able to operate without import cost penalties, and mid-sized plus smaller biotechs without the resources to sign MFN deals or onshore manufacturing facing margin compression. Trump has potentially created a caustic environment for smaller innovative players that may accelerate the timetable under which these players look to exit and suppress innovation. For what I call the “BioPharma Middle Class” (thinking of folks like Alnylam and Biomarin), they are all probably too big to get acquired and will now need to play ball with one hand tied behind their back. With Trump, the rules are clear: pay a dowry or I’ll make your life miserable.

FDA Clarifies GLP-1 Compounding Rules: Shortage-List Removal Means Enforcement — Hims & Hers in the Crosshairs

Source: Reuters / FDA.gov | Date: April 1, 2026

On April 1, 2026 — the same day the FDA approved Lilly’s FOUNDAYO — the agency issued a policy clarification stating that compounding pharmacies and outsourcing facilities may only produce copies of GLP-1 drugs while those drugs remain on the FDA drug shortage database; once removed from the shortage list, “essentially a copy” formulations face enforcement action. The clarification directly targets the multi-billion dollar compounded semaglutide and tirzepatide market that exploded during the shortage period, with platforms like Hims & Hers having built significant revenue on compounded GLP-1 access. The one-two punch of FOUNDAYO’s approval and this FDA clarification on the same day represents a coordinated signal that the era of compounded GLP-1 tolerance is ending.

BPS’ Take: This ruling might be the final warning for the compounded GLP-1 business model and will force telehealth platforms that built direct-to-consumer GLP-1 revenue streams off of them to rapidly pivot to authorized generics, branded partnerships, or entirely new product strategies (unfortunately that probably means a whole host of RFK-approved but untested peptides). This is a positive move for the drug industry and our IP protection. Hopefully, this additional scrutiny also forces more telehealth players to play within the rule of law on other issues, but after seeing how some of the new companies operate, I am less optimistic.

💰 FOLLOW THE MONEY

Deals, dollars, and what they signal

Biogen Acquires Apellis Pharmaceuticals for $5.6B — Rebuilding Its Complement and Immunology Franchise

Source: STAT News / BioPharma Dive / Biogen IR | Date: March 31, 2026

Biogen announced on March 31, 2026 the acquisition of Apellis Pharmaceuticals for $41.00 per share in cash (approximately $5.6 billion total), plus a contingent value right of up to $4.00 per share tied to SYFOVRE global net sales milestones of $1.5 billion and $2.0 billion between 2027 and 2031, for a total potential deal value of approximately $5.9 billion — sending Apellis shares up 136%. The deal adds SYFOVRE (pegcetacoplan, geographic atrophy, $587 million in 2025 sales) and EMPAVELI (PNH/C3G/IC-MPGN, $689 million in combined 2025 sales), bringing Biogen approximately $1.28 billion in combined acquired product revenue and rebuilding its complement/rare disease immunology franchise as its MS drug portfolio faces ongoing generic pressure. Biogen CEO Chris Viehbacher explicitly cited Apellis’s nephrology commercial infrastructure as a strategic accelerator for Biogen’s own felzartamab late-stage asset, with the first Phase 3 readout expected H1 2027; the deal is expected to close Q2 2026 and was one of two major acquisitions announced simultaneously on “Takeover Tuesday,” which drove the XBI index up 7% in a single day.

BPS’ Take: You can catch my full thoughts on this deal in my latest paid post (here). But in short, I think this is quite a savvy deal for Biogen. They’re paying roughly 2-3x peak sales for two strong commercial products. More importantly, they gain a commercial footprint in Nephrology, where Biogen has high hopes for felzartamab (acquired via Hi-Bio). Overall, this deal accelerates the future Biogen’s CEO Chris Viehbacher set out for it when he took over the company in 2022. Become less dependent on a dying multiple sclerosis business, and diversify beyond CNS diseases into Rare Disease and Immunology.

Eli Lilly Acquires Centessa Pharmaceuticals for Up to $7.8B — A Bold Bet on Sleep-Wake Neuroscience

Source: STAT News / Reuters / CNBC / NYT | Date: March 31, 2026

Eli Lilly announced the acquisition of Centessa Pharmaceuticals for $38.00 per share in cash (~$6.3B upfront), with an additional $9.00 per share CVR tied to FDA approval milestones for narcolepsy or idiopathic hypersomnia within five years. The deal’s total potential value of $7.8B represents a 38% premium and underscores Lilly’s aggressive expansion into the neuropsychiatry and sleep-wake neuroscience sectors.

The centerpiece of the deal is cleminorexton (ORX750), a potent, orally bioavailable orexin-2 receptor (OX2R) agonist currently in Phase 2 development, chasing Takeda’s oveporexton and Alkermes’ alixorexton to unseat existing standards of care like Pitolisant (Wakix), Solriamfetol (Sunosi), or stimulants like modafinil across narcolepsy and Idiopathic Hypersomnia.

BPS’ Take: The conversation around Lilly always centers around GLP-1s, but it is easy to forget that one of Lilly’s longtime core areas has been neuroscience. They have an approved Alzheimer’s drug after all, and a long history in Psychiatry among other areas. Lilly is showing that they are not afraid to open up the bag to bring in potentially best-in-class novel assets. This has been a company, who as of late has been in the rhythm of doing $1B - $3B deals. The up to ~$8B price tag signifies both Lilly’s patience in waiting for the right asset to send in a big offer on and the might of the forward looking GLP-1 revenues they expect. Lilly can basically buy pretty much anything under the sun given the run they are on. A lot of leadership teams would find it tempting to just go on a deal spree, but it is refreshing to see this company’s discipline even with their immense war chest.

Otsuka Acquires Transcend Therapeutics for $1.225B — Largest Psychedelic/Neuroplastogen Deal in Pharma History

Source: BioPharma Dive / Fierce Biotech | Date: March 30, 2026

Otsuka Pharmaceutical announced on March 30, 2026 the acquisition of Transcend Therapeutics for $700 million upfront plus up to $525 million in sales-based milestones, totaling a potential $1.225 billion — the largest acquisition in the psychedelic/neuroplastogen sector to date. The lead asset, TSND-201 (methylone-based neuroplastogen), holds FDA Breakthrough Therapy Designation, published Phase 2 data in JAMA Psychiatry, and has Phase 3 trials currently enrolling in PTSD. Otsuka, facing headwinds from generics competition to Abilify (aripiprazole), is doubling down on CNS/psychiatry with a differentiated mechanism targeting PTSD — a high-unmet-need indication where the FDA has been willing to grant Breakthrough Therapy Designation to novel neuroplasticity-based approaches; deal close is expected Q2 2026.

BPS’ Take: Otsuka’s $1.225B bet on TSND-201 legitimizes neuroplastogens as a serious pharmaceutical drug class and sets a new valuation benchmark for other potential players interested in entering the novel psychedelics space. This is also another data point that both large companies like AbbVie and smaller CNS specific players like Otsuka (or even Lundbeck) believe in the therapeutic potential of next-gen psychedelics, which look to improve upon their recreational predecessors. By acquiring a non-hallucinogenic neuroplastogen, Otsuka is also signaling an interest in potentially removing the "service-layer" bottleneck. They are betting that the FDA will grant a label that does not require intensive, supervised psychotherapy, which could be seen as a commercial advantage.

Back next week with another edition of LWTB! Stay tuned and hope you have a strong start to your week!

Biogen’s multiple sclerosis days are nearly long behind them. With the acquisition of Apellis , their transformation into a balanced commercial-stage neuroscience, rare disease, and immunology company is finally complete.

This is a natural course of company’s life in our sector. Regeneron was on the ropes while its EYLEA franchise faced generic erosion, but now they’re a major player in immunology and certainly a burgeoning player in oncology and other disease areas as well. Someone like Sanofi was once known for being a major player in insulin; that was their bread and butter. But eventually that bread and butter ran out, and they had to pivot into areas like immunology and specialty care.

Not everyone can be a Gilead or a Vertex , two companies who have sunk deep roots into HIV and Cystic Fibrosis, respectively, that continue to power their businesses today. Most companies need to shed or molt their skin and transform into something new at one point or another.

The Gradual Shift Away from MS

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Biogen’s metamorphosis didn’t just happen overnight; it started in 2022 with the hiring of CEO Chris Viehbacher, who formerly led Sanofi . The company’s legacy multiple sclerosis (MS) franchise faced major patent cliffs. TECFIDERA, which was once a multi-billion dollar behemoth, had been decimated by generic competition, causing sales to plunge nearly 50% in 2025 alone. TYSABRI too, which was Biogen’s long reliable blockbuster, faced biosimilar competition in the same year. To add insult to injury, Roche’s OCREVUS was sort of the primary predator that forced Biogen to need to molt, despite Biogen receiving royalties on this product from their prior collaborations with Roche. OCREVUS continued to grow and take market share from Biogen’s legacy portfolio while 2025 patent cliffs loomed in the distance.

Viehbacher rather quickly kicked off a “fit for growth” initiative in November 2022 netting in a 15% headcount trim and achieving $1B in gross savings. In addition to that, he did a top-to-bottom pipeline review and focused on finding anchor assets that were clinical stage and could eventually become meaningful revenue drivers for the company.

Through that strategic exercise, they decided to focus on building out their CNS rare disease portfolio, as well as their immunology pipeline (which at the time as really just one key asset), with a special focus though on nephrology indications. What this amounted to was a BD spree. Notably, in July 2023, they acquired Reata for $7.3B, gaining access to SKYCLARYS for Friedreich’s Ataxia. Later, they acquired Hi-Bio for $1.15B, adding felzartamab to fuel their entrance into the wide world of nephrology. These two acquisitions were also complemented by multiple R&D collaborations with smaller biotechs focusing on other diseases in the Rare Disease and Immunology buckets.

In January 2026, they continued their efficiency efforts, reporting a 26% spend reduction in R&D, culminating it what appeared to be a solid foundation for the future of the company. New product launches had offset the MS generic erosion declines of the past year, the company was running more efficiently, and had a pipeline set up for multiple near-term late-stage data readouts across newly prioritized disease areas.

This was a company setting up to change into something completely different. The future of the company was staked on assets completely foreign to what existed in 2022, when Viehbacher took over. The optionality from the pipeline came from new high-risk areas, but notably only one MS asset still existed in the pipeline (BIIB091, a peripheral BTK inhibitor). MS has taken a back seat and is now upside only. Out with the old. In with the new.

So even before the announced Apellis acquisition, Biogen was clearly set up to be a rare disease, immunology, neurodegenerative disease player. So why did Biogen acquire Apellis now?

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I really like the format John Oliver uses for his hit satirical news comedy show Last Week Tonight. The first half of his show usually reflects back upon the last week in the news, with Oliver delivering the comedic angle of all the crazy shit happening in our world.

I wanted to create something digestible and reflective like that, that also could serve as a vehicle to provide my unique perspective on the week in Biopharma. The format below is what I came up with. I am hoping to crank these out each week and have these in your in box on Sundays, while you are getting your ducks in a row for your Monday meetings. I envision this series being available to both free and paid subscribers, with paid subscribers continuing to get my regular deep-dive content.

These posts will have three sections with roughly three things in each bucket that caught my attention:

• Press Release Decoder: going beyond the company speak, reading between the lines, thinking about what isn’t being said, to illustrate the strategic implications of a company’s moves that don’t make it into the press release

• Connecting the Dots: looking at stories that are either about the macro or from the mainstream news and how they may impact BioPharma

• Follow the Money: quick takes on some key deals that were struck and what they mean for those companies, their competitors, or the sector at-large

I’ll keep iterating on this “Last Week Tonight” series with the hope of it getting better and more useful to you. You might see new sections beyond these initial three or slight tweaks, so please bear with me. Any feedback you have is welcome!

As always, if you are getting value out of my content and you want to take it to the next level, please consider becoming a paid subscriber 🙏🏾.

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📡 PRESS RELEASE DECODER

Going beyond the press release

Rhythm Pharmaceuticals — Imcivree (Setmelanotide) Approved for Acquired Hypothalamic Obesity: A First-in-Class Rare Disease Win

Source: BioPharma Dive | Date: March 23, 2026

The FDA approved setmelanotide (Imcivree) for adults and children 4 and older with acquired hypothalamic obesity (AHO), a condition caused by hypothalamic brain injury — making this the first-ever approved therapy for AHO. The Phase 3 TRANSCEND trial demonstrated approximately 18 percentage points greater weight loss versus placebo, leveraging the drug’s MC4R agonism mechanism, which is mechanistically distinct from GLP-1 receptor agonists. Analysts project a $1B+ market opportunity across an estimated 2,000–10,000 diagnosed U.S. patients; consensus 2026 estimates for the new indication sit at ~$40M, and RYTM shares rose approximately 6% on the news.

BPS’ Take: has really created a beachhead in rare obesities prosecuting a single MOA across multiple drugs in its pipeline. While it is dwarfed by the broader GLP-1-focused obesity population, adding up these rare obesity markets, as RYTM has done, can amount to sizable market potential over time in a relatively low-competition arena. They’re a solid example of how building a rare disease business can still be right at the intersection of patient-impact and market opportunity. They’ve been a popular buyout target off and on over the years, and if they are able to prove that rare obesities can be a blockbuster set of indications, larger players were be interested.

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Corcept Lifyorli (Relacorilant) + Nab-Paclitaxel — FDA Full Approval for Platinum-Resistant Ovarian Cancer: First SGRA Crosses the Finish Line

Source: FDA.gov / Fierce Pharma | Date: March 26, 2026

The FDA granted full approval to relacorilant (Lifyorli) combined with nab-paclitaxel for platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer — making it the first FDA-approved selective glucocorticoid receptor antagonist (SGRA) for any oncology indication. This decision came after a prior Complete Response Letter for the drug in hypercortisolism (due to hypertension AEs) and arrived ahead of schedule, placing Corcept in a competitive position against the entrenched ovarian cancer standard of care with no existing SGRA-class competition in the market. The approval validates a mechanism that had previously been considered commercially speculative and opens a new drug class in a space where options remain limited for platinum-resistant patients.

BPS’ Take: Going from seeing the door shut on one approval and winning another in a major indication is quite the victory. There was certainly negative sentiment swirling about the ovarian cancer approval in the wake of the CRL, but this is a great example of how the benefit-risk of a drug changes based on the indication. The FDA essentially said: "We can't approve this for 10,000 rare disease patients with hypertension concerns." But then said: "We absolutely can approve it for 50,000+ PROC patients where a 4-month OS extension is meaningful and safety profile is acceptable." LIFYORLI enters platinum-resistant ovarian cancer (PROC) as a potentially broad-based option in a market that has become fragmented by therapies for biomarker-driven sub-groups (folate receptor alpha, HRD). Folate-receptor alpha targeting ADCs, like ELAHERE, are probably most under threat by this new approval, as LIFYORLI can address the entire PROC population and not just the FR-alpha high group.

🌐 CONNECTING THE DOTS

When the mainstream meets biopharma and vice versa

Trump’s MFN Drug Pricing Policy: The Fine Print Reveals a Framework Designed to Raise Foreign Prices, Not Lower U.S. Costs

Source: STAT News | Date: March 24, 2026

An HHS official disclosed to congressional Republicans that the Most Favored Nation (MFN) drug pricing framework is explicitly designed to allow manufacturers to “price wherever you want” in the U.S. so long as they do not underprice American consumers in foreign markets — a framing that inverts the popular understanding of MFN as a cost-reduction tool. Sixteen major drugmakers have already reached agreements under the framework, and the 3-year deal terms may expire before many affected drugs even launch in foreign markets. The revelation suggests MFN is being operationalized as a foreign price-raising mechanism rather than a domestic price-control tool.

BPS’ Take: For biopharma manufacturers, this reframing of MFN is commercially significant: if the policy succeeds in elevating ex-U.S. prices toward U.S. reference levels, it could partially neutralize one of the sector’s greatest structural headwinds — international price arbitrage — while leaving U.S. pricing power intact.

RFK Jr. Signals FDA Will Legalize ~14 Restricted Peptides, Opening Gray-Market Therapies to Compounding Pharmacies

Source: Politico / NPR | Date: March 22–26, 2026

On Joe Rogan’s podcast (late February), HHS Secretary Robert F. Kennedy Jr. declared himself “a big fan” of peptides and signaled that the FDA will reclassify approximately 14 of 19 peptides currently on the agency’s restricted list — including BPC-157, ipamorelin, and MOTS-c — back to legal compounding status within weeks. Kennedy frames the move as reversing what he calls an “illegal” 2023 Biden-era reclassification that he argues drove patients toward black-market suppliers and overseas manufacturers. If enacted, compounding pharmacies would be permitted to produce these peptides under state pharmacy boards, potentially legitimizing a market currently worth billions in gray-market sales and moving human-use peptide treatments from research-labeled products to pharmaceutical-grade compounded drugs.

BPS’ Take: The argument from compounders and RFK allies is somewhat logical: people are already using these peptides (often sourced from China and sold illicitly), so legitimizing pharmaceutical-grade compounding is harm reduction. Most peptides (BPC-157, CJC-1295, AOD-9604) that are super popular in the man-o-sphere lack rigorous human clinical trial data and have theoretical safety risks (cancer from growth hormone peptides, organ damage, immune reactions). The logic of green-lighting a lot of these vs. not federally legalizing other drugs we actually do have a lot of clinical research on is missing me, but that is a rant for another day.

Back to peptides - we already have really poor regulation of the supplements market, and these peptides have been hawked with specious claims by social media influencers even before this ruling. Bad news. Letting companies like HIMS, who have demonstrated a penchant to fastpass medicines to patients and disregard all kinds of laws in the process is a really dangerous thing. The decision also creates some odd competitive pressure on Novo Nordisk and Eli Lilly’s GLP-1 business. If these other peptides are legalized, telehealth platforms like HIMS (which acquired a peptide facility in early 2025) can now manufacture and market these other peptides as alternative weight loss drugs (that don’t have the backing of “evil big pharma”) and potentially blunt GLP-1 sales (while also potentially harming patients). No formal FDA rule change has occurred yet, despite RFK’s announcement, the move remains at the intention/negotiation stage.

💰 FOLLOW THE MONEY

Deals, dollars, and what they signal

Merck & Co. Acquires Terns Pharmaceuticals for $6.7B — A Clear Post-Keytruda Signal in Hematology

Source: STAT News / Reuters / BioPharma Dive | Date: March 25–26, 2026

Merck will acquire Terns Pharmaceuticals at $53.00 per share in an all-cash transaction valued at approximately $6.7B in equity ($5.7B net of cash), with TERN-701 — an oral allosteric BCR::ABL1 TKI in Phase 1/2 development for chronic myeloid leukemia via the CARDINAL trial — as the primary asset driving the deal. Terns stock had surged approximately 6x over the prior six months, reflecting the market’s growing conviction in TERN-701’s potential best-in-class profile, and analysts are already flagging the possibility of rival bids. The acquisition deepens Merck’s hematology pipeline at a pivotal strategic moment as the company faces the looming patent expiration of Keytruda, its $25B+ blockbuster PD-1 inhibitor.

BPS’ Take: To be honest with you, CML was really off my radar. When I first started working in heme/onc I was told by my seniors that it was a solved problem. I was mostly under the impression that patients were rather well managed on the existing set of generic TKIs, notably GLEEVEC. But Terns’ story is a great example of how Oncology markets can turn into chronic disease markets. Even though patients can live a full life with existing treatments, there is still a risk of mutation driven relapse but also accumulation of toxicity from AEs over time. This explains why companies are willing to pay for "me-too" assets in diseases that looked "solved." The market isn't really about cure innovation anymore in these spaces, it's about managing a patient population with chronic disease.

CLL could be headed that direction, or perhaps is already there, with how strong the BTK inhibitor class has been and is becoming. In oncology, efficacy usually outweighs safety, but when efficacy tops out, it creates more room for companies to differentiate on safety, tolerability, and convenience, which is where Terns and Novartis’ asciminib come in.

On the Merck side of the coin, they clearly don’t feel like they’ve enough to fill the Keytruda patent cliff yet, so much so that they are interested in getting into heme/onc. I wonder if other high unmet need heme/onc areas like AML, MDS, and MF are on the table for them too.

Gilead Sciences Acquires Ouro Medicines for Up to $2.18B — Second Major Deal in Five Weeks as Autoimmune Pivot Accelerates

Source: BioPharma Dive / Reuters / WSJ | Date: March 23–24, 2026

Gilead will acquire Ouro Medicines for $1.675B upfront plus up to $500M in milestones, with the key asset being gamgertamig (OM336), a BCMA/CD3 bispecific antibody targeting autoimmune diseases; Galapagos co-finances 50% of the deal and receives Ouro assets and employees in exchange for up to 23% royalties, while Gilead retains global commercialization rights. The transaction follows Gilead’s $7.8B acquisition of Arcellx in February 2026 — making this the company’s second significant deal in approximately five weeks. Together, the two deals further Gilead’s efforts to diversify beyond their commercial dominance in HIV and growing Oncology business into auto-immune.

BPS’ Take: I guess the team finally has a product to develop? A savvy move by the folks to get Galapagos to pay for half this drug in this co-financing architecture. I guess you could argue this was Gilead’s money all along, since they own ~25% of Galapagos, have two board seats, and also gave them ~$4B upfront many moons ago when the two companies struck their fruitless R&D collaboration. Tomato, tomahto. Galapagos basically feels like Gilead’s EU R&D hub and if OM336 continues to look promising, it may just make mathematic sense for Gilead to acquire the remaining 3/4ths of the company vs. paying the 23% royalty.

Novartis Acquires Excellergy for Up to $2B — Second Major Deal in One Week as Allergic Disease Strategy Accelerates

Source: Reuters | Date: March 27, 2026

Novartis will acquire Excellergy for up to $2B in upfront and milestone payments for Exl-111, an anti-IgE biologic with longer half-life and tighter receptor binding than Xolair, targeting allergic diseases including potential food allergy applications. The deal marks Novartis’s second multi-billion-dollar acquisition in one week following the $3B Pikavation/Synnovation deal announced March 20, with close expected in H2 2026 pending regulatory clearance.

BPS’ Take: snuck this in on a Friday, but I thought this was far more interesting than the Pikavation deal they did earlier in the week. Novartis now joins Regeneron and (via the RAPT acquisition) as squarely targeting the Allergy space using an immune-mediated approach. All three companies are deploying quite different strategies (GSK has a better XOLAIR, REGN is combining a BCMAxCD3 with DUPIXENT, and this EXL-111 basically sequesters IgE) so it will be quite the race to watch to see which therapeutic approach wins out. Allergy treatment and prevention are massive market opportunities, and we shouldn’t be surprised if other Big BioPharma players move into this space via deals. The immune reset read-through from antibody based therapies in autoimmune diseases is real, and this area is a high priority for the current HHS administration to boot, meaning if you’re a drug developer, you may get the FDA red carpet treatment (vs. the unpredictable 180s we’ve been accustomed to with this administration).

Hope you enjoyed this first edition of “Last Week Tonight in Biopharma”. As this gets going a bit more, please send through any constructive feedback.

Have you noticed we have more tech people in Biotech now? Over the past few years there has been an influx of people from the software world becoming interested in our space. You have the group of longevity-curious tech CEOs bankrolling anti-aging companies (e.g. Bezos, Altman, Armstrong), large tech companies focusing some of their R&D on drug applications (Nvidia, Microsoft, Google), former software people becoming biotech founders (InSitro, XtalPi, InSilico), and traditionally tech/generalist-focused funds funding drug companies.

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Why Tech Capital Is Fleeing Software (and Coming to BioPharma)

You don’t need an oracle to tell you that AI has played a major role in this trend. But why now?

The main reason I see is that the trajectory of AI has shown us that things like software—the field these individuals typically come from—is quickly collapsing into a world that will be commoditized. We hear stories every day, discussing how AI can be applied in the hands of their own engineers. A “super engineer” with agentic capabilities that can now deploy hundreds of AI-based engineers and orchestrate development across a number of different coding tasks simultaneously. Companies in the tech sector praise how many tokens their engineers use, asking them to continually use more and more.

On the flip side, we see many stories about how tech companies are now contracting their workforces—getting rid of lower-level engineers, QA, and QC—unnecessary functions that they anticipate will no longer be required in a more fully AI-integrated world.

This was always going to be the end state. AI was invented on the computer and trained on the internet, which in some respects is the most complete example of human thinking that we have. All of these models were coded in languages created by humans. In a sense, coding is perhaps one of the most familiar things to AI models because it is exactly what they are built on. If AI was a car, humans would be the end-to-end manufacturer of it. We built every part, bolted them together, and made it run.

Scale the software future up to its final destination. Why would a large multinational corporation buy enterprise software from someone like Workday or Salesforce when in the very near future—and perhaps even now—they could deploy one engineer to create custom software for their entire organization with the help of an army of AI bots? Following this thread, you can quickly see that software is going to be a commodity in the new world. Businesses (and consumers) will be able to easily and cheaply build the software tools they need.

Perhaps the same could be said of things that we use on a day-to-day basis in biotech strategy: Excel models, slides, curated databases, and other complex documents. It is becoming ever more clear that the value of an individual producing those versus an AI is shrinking considerably. The future of deliverable-based work in our space is going to be more about an individual orchestrating several AI-based “analysts” to produce the necessary deliverables that will feed into a strategic synthesis by the human orchestrator.

So if software is going to be a commodity, it makes sense for tech capital to flee traditional software-based companies and reallocate elsewhere. And where might that be? Well, it’s in areas like biotech, where the rules are far more complicated and there still remains a ton of room for AI to add value. Unlike software, where humans created the underlying language and understand its intricacies well, in the field of biology, we were not born with instruction manuals. By some measures, we perhaps only know 10% of the rules that govern our bodies. Moreover, those rules are exposed to the pressure of evolution; they are dynamic and will likely change over the course of our species. In the car analogy, we are even less than mechanics. In some sense, we are still trying to figure out what we’re actually driving.

As we know, in biotech, it’s really hard to develop novel drugs, another reason why we are seeing a whole host of new companies spin up that are well-funded but focusing on pre-existing targets (aka “well-validated biology”). Areas like biotech, where there are still incredible amounts of unknown, are the perfect places for new AI-focused capital to come into. We’re already seeing the biggest companies in our space discuss how AI is accelerating some of the more low-hanging operational fruit in their businesses.

But quickly we’re seeing the potential of how AI can be used to speed up drug discovery, document writing, finding optimal clinical trial sites, and a whole host of other blocking and tackling type tasks that go into drug development. Don’t get me wrong, we’re not at the era yet where AI can develop a drug “soup to nuts” on its own. That 10% of known biology is still a really big barrier. There’s no replacement for doing true discovery work and pushing the boundaries of what we know about biology to discover new rules that govern our cells, organs, and systems.

There is also no replacement for running clinical trials. We need to test more novel biology in human subjects to get a truer understanding, and more importantly, better data that we can feed back into the multitude of specialized AI models that are coming out. Only then will we get closer and closer to “simulating human biology”.

A Story About a Dog that Illustrated a Narrative Gap

Lately, we've seen some interesting stories pop up in the mainstream news about people in the tech world applying basic AI tools to develop new medicines. The one that stands out the most to me is the story of the Australian tech entrepreneur, Paul Conygham, who used AI tools—including large language models and protein structure prediction software—to help design a custom DNA cancer vaccine tailored to his dog Rosie's tumor. Thankfully, Rosie's health has significantly improved after receiving this bespoke cancer vaccine.

However, the responding commentary on social media was somewhat triggering for me. There was a group of people saying, "Why can't we do this for all cancers?" or "Look, this guy just cured cancer using AI; this completely changes everything and the pharmaceutical industry is upended." Even worse, some took this case as evidence that drug companies are intentionally withholding cures or not applying technology in a patient-centric way.

As insiders, we know that perspective is misguided. Even in Rosie's case, she didn't have a complete response or total eradication of all tumors, and we need longer follow-up to see how effective the therapy was. While it was a remarkable feat, it lacks the context that this work is already being done at a much larger scale in human patients. A number of cancer vaccine studies are already in clinical trials, most notably led by mRNA manufacturers like BioNTech and Moderna, which are in phase 3 studies with promising phase 2 data to support them.

This situation made it clear to me that in biotech, we have an issue communicating the promise of our technologies to a wider audience, whereas tech leaders are able to do this much more expertly. Solving this problem is incredibly critical, especially as we see more tech people entering biotech riding the wave of AI innovation.

What We Can Learn From the Tech Bros

I think it’s important to say that we shouldn’t shun tech folks from coming into biotech. There is much more we can gain by melding the best of our expertise and cultures together.

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Last month, Sanofi announced that they would be moving on from CEO Paul Hudson and bringing on Merck KGaA’s CEO Belén Garijo to take over for him.

This change made me think a bit about Hudson’s performance relative to other CEOs, to figure out whether his ousting was warranted given his performance. In truth, I had forgotten that he had been in the role for as much time as he had (6.5 years). Going down that rabbit hole was interesting enough for me to expand this into a broader exercise examining CEO performance across a couple simple metrics.

So today we’ll take a quick look at the beginnings of this analysis. If it is interesting enough to you I’ll continue to build on this data set and add new layers (e.g. CEO pay/compensation, pipeline data, etc.) that will help uncover deeper insights into the relative performance of our sectors most impactful executives.

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Overview of Methods

Before we get to the more interesting findings, I want to discuss the methodology: how I collected this data, what is included in the analysis, and the current limitations.

First off, this dataset is comprised of 23 different CEOs spanning companies including AbbVie, Amgen, AstraZeneca, Biogen, Bristol Myers, Eli Lilly, GSK, Gilead, J&J, Merck, Novo Nordisk, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, Vertex, Bayer, and Merck KGaA.

The dataset looks at each CEO from their starting point all the way through to today. For certain companies—particularly ones like AbbVie, Novo Nordisk, and GSK that have had CEO changes during that period—I try to capture data from both CEOs individually. For CEOs who are new to their roles, they obviously won’t have as much data to go off of. For the most part these CEOs were excluded from substantive analyses. For Regeneron’s CEO, Len Schleifer, I had to start his data from 2012. This is partly because if I started it from 1988 when Regeneron was founded (or even 1991 when Regeneron IPO’d), it would make the data look a little wonky, but also because it was impossible to find correct financial data from back then.

Quantitative Data

The main pieces of data I collect, examine, or generate are:

• Market Cap: While not a perfect metric, how much a company grows or shrinks during a CEO’s tenure serves as a rough quantitative barometer of their performance.

• Tenure Milestones: I captured the market cap on the beginning date of each CEO’s tenure, as well as on their last day (or current day, if they are still in the role).

• Intervening Data: I collected market cap data at the end of each intervening year during their tenure

• Value Created and absolute growth percentage: This measures the raw growth in market cap from start to finish for each CEO.

• Compound annual growth rate (CAGR): functionally ignores yearly fluctuations and calculates a “smooth” rate of return of market cap growth or decline for each CEO’s tenure.

Certainly there were other metrics that we could have looked at—and I hope to layer these in for future analyses—but some limitations here are that I didn’t look at things like EBITDA, EPS, other profit metrics, or revenue growth. Those are all things that I hope to include in the future, but for simplicity on the quantitative side, I focused really just on market cap.

Qualitative Data

Qualitatively, I tried to capture a few different things. Obviously, CEOs don’t take over brand-new companies; the case of Regeneron aside, most of these CEOs are taking over companies that are dozens of years old with a previous track record and history. Not every CEO is dealt the same starting hand, so to speak.

For each CEO, I tried to provide a qualitative score of 1 through 5—what I’m calling a QHS (Qualitative Health Score). This is a highly subjective metric, but effectively, I tried to assess the forward-looking health of the business when the CEO stepped into their role and compare that to what the future outlook of their businesses looks like today (or at the time they ended their role as CEO).

To attribute a QHS score I looked several factors, including but not limited to:

• Revenue and pipeline diversification (or over-concentration)

• External and internal sentiment about the company

• Sales trends for major products

• Patent cliff risk and sufficiency of maneuvers to delay or fill them

• Pressure to execute M&A, major deals completed, and where possible, the success or shortcomings of those deals in contributing to revenue growth

• Major outliers in the balance sheet (e.g., companies carrying lots of debt)

The goal was to effectively provide a a “vibe check” for the compare right before the CEO took office and what that vibe looks like today.

The larger table above includes information that you can read through, discussing my determinations of what the company state was at the start, as well as the rationale for the QHS score change. However, this scorecard, so to speak, does a more simplified job of showing you which CEOs improved, declined, or had stable QHS scores over the course of their tenure, based on my qualitative attributions.

Notably, most CEOs remained relatively stable in terms of their QHS scores. You had a range of cases here. Some cases like Bayer, which started off at a QHA score of 1 in overall pretty poor health and continued to stay there. Bayer, as we know, was saddled with a significant amount of debt following the Monsanto acquisition and was also tied up in a legal battle with several class action lawsuits related to Roundup. They had a declining pharma business and have struggled to generate growth, remaining “down in the dumps” while awaiting a turnaround.

At the other end, companies like Vertex—whose CEO, Reshma Kewalramani, took over a company with very bright prospects, especially in cystic fibrosis where Vertex is the unchallenged leader—continued to maintain a positive outlook for the company over the course of her tenure, including multiple late stage programs in new areas like pain, genetic medicines, cell therapy, and rare disease, thus far.

The biggest riser here, to no surprise, was AstraZeneca. Pascal Soriot’s story involves taking over the company when it was significantly beaten up and facing multiple patent cliffs for major products. He orchestrated a turnaround story that many other Big Pharma teams use as an example to follow.

The other is obviously Dave Ricks at Eli Lilly, who—largely because of the multiple successes in GLP-1-based assets—has now helped Lilly reach the status of being the first trillion-dollar healthcare company.

With that out of the way, let’s look at a few different data visualizations from this dataset and tease out some insights about CEO performance.

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Charts! Charts! Charts!

I think the most digestible way to look at some of this data is by grouping the CEOs into cohorts. I organized their performances into these cohorts based on how much time they have spent in their role:

• Short tenure: less than 4years

• Medium tenure: 4 to 10 years

• Long tenure: 10 years and over

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In this episode, Shivu and Kenny discuss how you as a caregiver or patient can use public resources like clinicaltrials.gov and Large Language Models (LLMs) like ChatGPT to discover the latest treatment options for a particular disease and empower yourself to have a more productive conversation with your doctor. Kenny and Shivu discuss an example of this situation from an episode of Apple TV’s “Shrinking”, starring Harrison Ford. In the episode they go through a demo of how they would find new treatment options for Ford’s character, a patient suffering from Parkinson’s Disease who has exhausted all available treatment options.

CHAPTERS

00:00 Introduction to Clinical Trials

03:04 The Importance of Patient Involvement

06:13 Navigating Clinical Trials: A Practical Guide

09:06 Using AI to Enhance Patient Care

11:53 Drafting Effective Communication with Doctors

14:27 Empowering Patients Through Knowledge

17:46 Finding the Right Treatment Options

20:30 The Role of Research in Patient Advocacy

23:03 Conclusion and Future Directions

34:38 Outro

Questions? Email us at: ⁠⁠mailto:drugdealinpod@gmail.com⁠⁠
Follow ⁠Shivu on X⁠(@bigpharmasharma): https://x.com/BigPharmaSharma
Sign up for Shivu’s newsletter: https://www.bigpharmasharma.com/⁠ ⁠
Follow ⁠Kenny⁠ on Linkedin: https://www.linkedin.com/in/kennylalwani/

DISCLAIMER: The views and opinions expressed in this podcast are for informational and educational purposes only. They are not intended as medical advice and should not be used as a substitute for professional medical judgment or guidance. Always consult a qualified healthcare provider with any questions you may have regarding a medical condition or treatment.

If you are a close watcher of the cell therapy field, as I am, by now you’ve heard that Gilead acquired Arcellx for an implied value of $7.8B. The deal includes an additional $5 per share contingent value right (CVR) if the companies’ BCMA CAR-T program, anito-cel, is able to achieve $6B+ in sales by the end of 2029. It also comes at at 68% premium to Arcellx’s 30-day volume-weighted average (VWAP) share price as of February 20, 2026.

If your news feeds are anything like mine, you’ve also probably been inundated with a copious amount of room temperature AI-slop on this deal (especially in the “HR App”). Nearly all of these “analyses” are basically extrapolations of abstractions from the press release. All of these condense down to some form of, “This deal reflects Gilead’s conviction in anito-cel! Big Pharma interest in autologous cell therapy has been reinvigorated! This will open up the gates for more auto cell therapy acquisitions!”.

Now that that’s out of the way we can start talking specifics. As someone who has spent a large chunk of his career shaping strategy in the effort to advance ex vivo cell therapy products (including at Gilead/Kite), I would love for this acquisition to mean that this class, especially autologous, are back in vogue writ-large. The reality, reflected in the details and context leading up to this deal, paint a different story.

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Understanding the ‘Why Now?’

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If you haven’t checked the vibes in the room, the entire BioPharma community is in an uproar at Center for Biologics Evaluation and Research (CBER) director Vinay Prasad’s latest action. Per reports, Moderna received the rare refusal-to-file (RTF) letter from CBER after using a precious priority review voucher (PRV) for its mRNA-based influenza (flu) vaccine, mRNA-1010. It appears this wasn’t a group decision either. Prasad unilaterally decided to issue the RTF, while his reviewers were in support of accepting Moderna’s filing for review.

In the RTF (which Moderna released here), Prasad esentially says that Moderna’s application is incomplete because it lacks an appropriate comparator, namely that the main study used in Moderna’s filing package (called P304) examining adults ages 50 years old and older, was comparing Moderna’s drug to standard-dose flu vaccine, instead of the high-dose flu vaccine, which is recommended in use for the 65 and older group.

But Moderna is mad because they already had confirmation from the FDA that their design was acceptable, and further addressed questions about comparison to high-dose vaccines with supplementary Phase 3 immunogenicity data. Based on Moderna’s recounting of their interactions, they were given no reason to believe that their filing would not at least be reviewed. You usually don’t spend a PRV (which fetch $100-$200M on the open market) unless you felt high confidence in your application being accepted.

Prasad (and his boss Marty Makary, head of the FDA) defended the decision, effectively arguing that a high-dose comparator should have been used in the main study for 65+ age group because that is the current standard of care in the US (although not in much of the rest of the world).

This latest saga at the FDA involving Vinay Prasad seems like more of the same, but there are far reaching implications to this action that the BioPharma sector should consider.

A Major Setback for Vaccine Development and Investment

Moderna is left swimming up stream without a paddle. They ran multiple 40K+ size global studies all to have the FDA basically say their studies are effectively useless and not even worth considering. That’s obviously millions of dollars flushed down the drain and a steel vault door shut in the face of America’s leading mRNA manufacturer.

More importantly, it’s one less effective medicine available for patients, not just for this flu season (which has been quite severe) but many flu seasons to come. Moderna has come out and said that they aren’t even going to continue investing in P3 vaccine trials for infectious diseases in the US or anywhere else. While they will still likely take mRNA-1010 into international markets, it doesn’t make financial sense for the company to continue pursuing these sorts of vaccines if the US market is going to be off limits to them.

Of course some of this commentary is posturing by Moderna's CEO, but I don't blame him. Vaccines are unique in how heavily the US market subsidizes global access. American reimbursement rates and market size essentially bankroll the development and distribution pipelines that supply the rest of the world. Cut off US market access for mRNA vaccines, and the economics collapse for Moderna domestically and for every international market counting on these products. If Moderna follows through on retreating from infectious disease development, foreign regulators may not have as many mRNA vaccines to approve. The only salvage pathway would be out-licensing to partners willing to shoulder the clinical and commercial burden ex-US. This is a scenario that delays timelines, fragments supply chains, and ultimately could leave patients waiting longer for innovation.

Why should any other mRNA vaccine developers feel differently? Each of them, certainly smaller and less financial endowed than Moderna, is probably thinking the same thing. Is it worth continuing to pursue our infectious disease programs?

Investors too could be more likely to shy away from mRNA plays as well. The FDA’s shifting standard and lack of predictability adds immense late-stage to risk. No investor wants to fork over tens of millions of dollars only for their portfolio companies major inflection catalyst to be rendered moot because of a sudden unpredictable change in opinion at the FDA. This lack of consistency reverberates through all levels of the BioPharma ecosystem.

Miscommunications Abound

It is important to look at the timeline of events here to really understand what went wrong and why. And what stands out is a clear communication issue.

There is a disconnect between the higher ups at the FDA, like Prasad and Makary, and long-time staffers who work under them. From the outset in April 2024, the vaccine team at the FDA defines Moderna’s trial design as “acceptable” but “recommends” they use high-dose. Moderna opts to go the standard-dose route that was deemed “acceptable”. Prasad gets involved on this project after the study has already started (July 2025) and raises concerns. By August, FDA staff tell Moderna that the lack of a high-dose group in the control arm is going to be a “significant issue” (assuming that they got verbal guidance from Prasad on this here and are trying to flag that for Moderna) and requests additional analyses, which the company provided. This included data from a separate Phase 3 study comparing mRNA-1010 with a high-dose flu vaccine, but focusing on antibody levels rather than actual efficacy. Prasad has long been a critic of immunogenicity data as a substitute for outcomes in the approval of vaccines, and releases several internal FDA memos guiding the agency to move away from valuing these sorts of data points for approval.

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Summary

In this episode, Shivu and Kenny review their predictions for 2025 and make new predictions for 2026. They discuss trends in mergers and acquisitions, market performance, the impact of AI in drug development, and the rise of digital advertising in the pharmaceutical industry. They also explore the evolving landscape of biotech companies, regulatory changes from the FDA, and the growing interest in metabolic diseases and psychedelics. Finally, they introduce the ‘pharm to table’ model in pharma, emphasizing direct-to-patient commercial channels and how these increase patient agency.

Chapters

00:00 Introduction and Overview of Predictions

04:37 Grading 2025 Predictions

10:35 Shivu’s 2025 Predictions and Grades

16:53 2026 Predictions: Emerging Trends

22:50 Regulatory Landscape and the FDA’s Role

30:46 Predictability in Drug Approval Processes

30:51 The Metabolic Space and GLP-1s

33:08 Big Pharma’s Entry into Obesity and Diabetes

34:56 The Risk of Commoditization in Drug Markets

37:06 Differentiation in the GLP-1 Market

39:40 The Rise of Psychedelics in Psychiatry

47:21 Pharm-to-Table Model in Pharma

54:06 Empowering Patients through Direct Access

DISCLAIMER: The views and opinions expressed in this podcast are for informational and educational purposes only. They are not intended as medical advice and should not be used as a substitute for professional medical judgment or guidance. Always consult a qualified healthcare provider with any questions you may have regarding a medical condition or treatment.

JPM is always a tone-setter for the year in BioPharma. Everybody tunes into what the biggest companies in our space have to say. What’s their M&A appetite? How are they thinking about China? What about Trump? Platforms or Products? Their commentary dictates how other parts of our sector view their own businesses.

At some level, our sector is the truest expression of 'trickle-down economics.' When Big Pharma decides to buy or partner, that capital recycles back into VCs and public investors, eventually funding the next generation of Series A startups. More M&A at the top means bigger and more exits, and may in turn influence a functional IPO window and a reason for early-stage investors to keep writing checks.

So every year what is said during this week is important, even if it feels like there are less and less people hovering around San Francisco during this time of the year. The streets are less lively. The random bump-ins are less frequent. The after-parties have more elbow-room. Still the tone is set from the top - and that’s what today’s post is all about.

I dug through transcripts and slides from all the Big Biopharma companies1, connected the dots, and pulled out several key themes, insights, and implications that portend to shape the year ahead. Let’s get into it.

M&A Philosophy Divide

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Often times you hear a lot of the same talking points on key topics across the Big Biopharma CEOs. M&A can sometimes fall into this category. “We’re interested in bolt-on deals”. “We have an appetite for late-stage de-risked assets”. “We like pipeline-in-a-product type deals with clinically de-risked programs”. Certainly we’ve heard all that before and heard versions of that even at this JPM.

The real striking divide this time around was M&A philosophy. The matrix I created above is a helpful framing for where each major players sees themselves with regards to their desire to do deals and their LOE exposure (% of 2025 revenues facing erosion in the next 5 years).

Most companies sit in the bottom right quadrant, called “Growth Opportunists”. They have relatively moderate to low LOE exposure over the next five years, strong balance sheets, and are able to do deals more selectively with less pressing need for large late-stage acquisitions that bring in near-term revenues. They can jump into big meaty transactions if they want to, but it’s not as pertinent. It’s perhaps surprising to see a company like AbbVie and Roche in this quadrant, however both companies are largely past their major patent cliffs, digesting previously large acquisitions or big partnerships, and cultivating those programs now in-house.

The more interesting groups sit in the other three quadrants though.

In the top right you have companies (I am calling ‘Crisis Responders’) who have the highest percentage of their revenues threatened by patent cliffs and have naturally been the most acquisitive, and would seem to continue to be given their JPM commentary. BMS and Merck aiming to fill the forthcoming PD-1 revenue gaps with their slurry of late stage acquisitions are great examples of an aggressive external innovation strategy. Others in this group, like J&J and Amgen who do have rather significant revenues at risk over the next five years, appeared more balanced in their internal/external innovation split, and are more focused on early stage deals (per their comments) with optionality for larger deals if the right one comes up. Still, in those cases, deals to build the pipeline will likely play a roel

In contrast to this group sits Regeneron, a lone ranger of sorts. Its commercial revenues are at a relatively high (~30%) LOE risk, but their management made it a point to take a contrarian position against large-scale M&A, arguing that such deals lead to “value destruction”. Instead, Regeneron is betting on themselves, focusing 95% of its R&D resources on internal programs to organically grow out of oncoming patent cliffs and formulation strategies like transitioning its retina franchise from EYLEA to EYLEA HD to mitigate biosimilar erosion (note: it appears they are looking to take forward a similar strategy to stave off DUPIXENT patent cliffs in 2030).

As a strategy guy, I love that Regeneron came into JPM with such conviction on their plan. It shows a deep evaluation both of their own company strengths (which has long been their proprietary genetic and antibody platforms) and performance of their peers’ strategies. Regeneron is uniquely equipped to organically grow out of their patent cliffs, because of the strength of their platforms and they know it.

The bottom left, “organic innovators” bucket, is an interesting one too and tells a tale of two stories. On the one hand you have companies like Vertex and Lilly who are well equipped with cash-printing machines (GLP-1s and CF franchise), and have redeployed that capital heavily towards internal R&D but also towards select bolt-on product acquisitions and platform buys that can enhance R&D capabilities. If Regeneron is the home chef that is so good at cooking that eating out would just be a waste of money, Vertex and Lilly are equally talented home chefs, but love a nice fine dining tasting menu every once in a while. Had either of these companies been in the same LOE situation as Regeneron, they probably would also be telling the JPM crowd that they didn’t feel a significant urgency to do big deals, because their R&D engine has had a strong track record of hitting home runs. They could organically grow through their cliffs and pull the trigger on a big deal only if it really made a ton of sense.

On the other hand you have folks like Bayer and Takeda who I think would love to be able to do more deal, but really can’t because they are saddled with debt and/or insufficient firepower. In turn, they are more focused on growing their existing internal portfolios and making the most of what they have now.

An easy takeaway from this chart is that the right half of the slide are going to be your active buyers, bidding each other up and out for the next great product, while the companies on the left will be more or less staying put.

Policy Overhang Resolution: IRA, MFN, Tariffs

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Welcome back! I hope all of you experienced a restful holiday and are having a strong start to the new year. January in Biopharma is signified by the JP Morgan Healthcare Conference (JPM). This is where deal discussions begin for the coming year and also where major deals get announced. Anecdotally, we have seen M&A appetite from Big Pharma/Biotech pick up over the last few years. Buzz and rumors are accordingly picking up as well. Much of this has to do with everyone’s favorite two words [pause for effect]: Patent Cliffs!

2026 will be marked by healthy M&A activity from the top 15-20 or so players in our sector. And to that end, I thought a great way to kick off the year headed into JPM is to highlight who I think has a strong chance of getting acquired this year. Below I’ve stated the case for six companies (and maybe a bonus one or two) that I think will be acquired over the course of 2026.

If you enjoy strategic analyses, insights, and opinions about Biotech and Pharma from an insider’s perspective, you can get access to all Big Pharma Sharma content by becoming a paid subscriber. Thanks for your support!

2026 will be marked by healthy M&A activity from the Top 15-20 or so players in our sector. And to that end, I thought a great way to kick off the year headed into JPM is to highlight who I think has a strong chance of getting acquired this year.

Below I’ve stated the case for six companies (and maybe a bonus one or two) that I think will be acquired over the course of 2026.

If you enjoy strategic analyses, insights, and opinions about the Biotech and Pharma from an insider’s perspective, you can get access to all Big Pharma Sharma content becoming a paid subscriber. Thanks for your support!

Subscribe now

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